Randy D. Blakely, Ph.D.

Professor

randy.blakely@vanderbilt.edu

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Faculty Appointments
Professor of Pharmacology Professor of PsychiatryAllan D. Bass Chair in Pharmacology
Education
Ph.D., Neuroscience, Johns Hopkins University, Baltimore, MarylandB.A., Philosophy, Emory University, Atlanta, Georgia
Office Address
7140 MRB III
Center for Molecular Neuroscience
Nashville, TN 37232-8548
Research Description
Once released into the synaptic cleft, neurotransmitters like serotonin (5HT) and norepinephrine (NE) must be quickly removed to limit the magnitude and duration of chemical signaling. The principal mechanism for 5HT and NE clearance is active transport back into neuronal terminals. Drugs with important clinical or addictive properties, including antidepressants, cocaine and amphetamines, block the access of 5HT and NE to transport sites and thus prolong their action. Using chimera studies and site-directed mutagenesis, we are exploring structural domains that lead to neurotransmitter and antagonist specificity for 5HT and NE transporters. With site specific antibodies and electrophysiologic techniques, we are evaluating post-translational mechanisms involved in acute carrier regulation in vitro and in vivo. Finally, we are exploring the effects of targeted transporter mutations using transgenic mice as a model for the behavioral and neurologic consequences of transporter defects in humans.
Research Keywords
molecular neuroscience and neurogenetics linked to brain targets of psychostimulants and antidepressants and neurotransmitter inactivation
Publications
Raj V, Haman KL, Raj SR, Byrne D, Blakely RD, Biaggioni I, Robertson D, Shelton RC. Psychiatric profile and attention deficits in postural tachycardia syndrome. J. Neurol. Neurosurg. Psychiatr [print-electronic]. 2009 Mar; 80(3): 339-44. PMID: 18977825, PMCID: PMC2758320, PII: jnnp.2008.144360, DOI: 10.1136/jnnp.2008.144360, ISSN: 1468-330X.

Kaufmann KW, Dawson ES, Henry LK, Field JR, Blakely RD, Meiler J. Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies. Proteins. 2009 Feb 2/15/2009; 74(3): 630-42. PMID: 18704946, PMCID: PMC2782712, DOI: 10.1002/prot.22178, ISSN: 1097-0134.

Carneiro AM, Airey DC, Thompson B, Zhu CB, Lu L, Chesler EJ, Erikson KM, Blakely RD. Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2009 Feb 2/10/2009; 106(6): 2047-52. PMID: 19179283, PMCID: PMC2632716, PII: 0809449106, DOI: 10.1073/pnas.0809449106, ISSN: 1091-6490.

Prasad HC, Steiner JA, Sutcliffe JS, Blakely RD. Enhanced activity of human serotonin transporter variants associated with autism. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2009 Jan 1/27/2009; 364(1514): 163-73. PMID: 18957375, PMCID: PMC2674096, PII: Y48156200R3J885Q, DOI: 10.1098/rstb.2008.0143, ISSN: 1471-2970.

Steiner JA, Carneiro AM, Wright J, Matthies HJ, Prasad HC, Nicki CK, Dostmann WR, Buchanan CC, Corbin JD, Francis SH, Blakely RD. CGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake. Mol Brain. 2009; 2: 26. PMID: 19656393, PMCID: PMC2731736, PII: 1756-6606-2-26, DOI: 10.1186/1756-6606-2-26, ISSN: 1756-6606.

Matthies HJ, Han Q, Shields A, Wright J, Moore JL, Winder DG, Galli A, Blakely RD. Subcellular localization of the antidepressant-sensitive norepinephrine transporter. BMC Neurosci. 2009; 10: 65. PMID: 19545450, PMCID: PMC2716352, PII: 1471-2202-10-65, DOI: 10.1186/1471-2202-10-65, ISSN: 1471-2202.

Zhao J, Matthies DS, Botzolakis EJ, Macdonald RL, Blakely RD, Hedera P. Hereditary spastic paraplegia-associated mutations in the NIPA1 gene and its Caenorhabditis elegans homolog trigger neural degeneration in vitro and in vivo through a gain-of-function mechanism. J. Neurosci. 2008 Dec 12/17/2008; 28(51): 13938-51. PMID: 19091982, PMCID: PMC2660329, PII: 28/51/13938, DOI: 10.1523/JNEUROSCI.4668-08.2008, ISSN: 1529-2401.

Carvelli L, Blakely RD, DeFelice LJ. Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Sep 9/16/2008; 105(37): 14192-7. PMID: 18768815, PMCID: PMC2528871, PII: 0802214105, DOI: 10.1073/pnas.0802214105, ISSN: 1091-6490.

Steiner JA, Carneiro AM, Blakely RD. Going with the flow: trafficking-dependent and -independent regulation of serotonin transport. Traffic [print-electronic]. 2008 Sep; 9(9): 1393-402. PMID: 18445122, PMCID: PMC2773847, PII: TRA757, DOI: 10.1111/j.1600-0854.2008.00757.x, ISSN: 1600-0854.

Mazei-Robison MS, Bowton E, Holy M, Schmudermaier M, Freissmuth M, Sitte HH, Galli A, Blakely RD. Anomalous dopamine release associated with a human dopamine transporter coding variant. J. Neurosci. 2008 Jul 7/9/2008; 28(28): 7040-6. PMID: 18614672, PMCID: PMC2573963, PII: 28/28/7040, DOI: 10.1523/JNEUROSCI.0473-08.2008, ISSN: 1529-2401.

Hahn MK, Blackford JU, Haman K, Mazei-Robison M, English BA, Prasad HC, Steele A, Hazelwood L, Fentress HM, Myers R, Blakely RD, Sanders-Bush E, Shelton R. Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depression. Genes Brain Behav [print-electronic]. 2008 Jun; 7(4): 487-95. PMID: 18081710, PMCID: PMC2670227, PII: GBB384, DOI: 10.1111/j.1601-183X.2007.00384.x, ISSN: 1601-183X.

Carneiro AM, Cook EH, Murphy DL, Blakely RD. Interactions between integrin alphaIIbbeta3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans. J. Clin. Invest. 2008 Apr; 118(4): 1544-52. PMID: 18317590, PMCID: PMC2260909, DOI: 10.1172/JCI33374, ISSN: 0021-9738.

Orndorff RL, Warnement MR, Mason JN, Blakely RD, Rosenthal SJ. Quantum dot ex vivo labeling of neuromuscular synapses. Nano Lett [print-electronic]. 2008 Mar; 8(3): 780-5. PMID: 18237149, DOI: 10.1021/nl072460x, ISSN: 1530-6984.

Kim CH, Waldman ID, Blakely RD, Kim KS. Functional gene variation in the human norepinephrine transporter: association with attention deficit hyperactivity disorder. Ann N Y Acad Sci. 2008; 1129: 256-60.

Henry LK, Blakely RD. Distinctions between dopamine transporter antagonists could be just around the bend. Mol Pharmacol. 2008; 73((3)): 813-23.

Misawa H, Fujigaya H, Nishimura T, Moriwaki Y, Okuda T, Kawashima K, Nakata K, Ruggiero AM, Blakely RD, Nakatsu F, Ohno H. Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice. Eur J Neurosci. 2008; 27((12)): 3109-17.

Hoard JL, Hoover DB, Mabe AM, Blakely RD, Feng N, Paolocci N. Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase A and p75. Neuroscience. 2008; 156((1)): 129-42.

McDonald PW, Hardie SL, Jessen TN, Carvelli L, Matthies DS, Blakely RD. Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of dopamine mediated by synaptic localization of the dopamine transporter DAT-1. J. Neurosci. 2007 Dec 12/19/2007; 27(51): 14216-27. PMID: 18094261, PII: 27/51/14216, DOI: 10.1523/JNEUROSCI.2992-07.2007, ISSN: 1529-2401.

Henry LK, Meiler J, Blakely RD. Bound to be different: neurotransmitter transporters meet their bacterial cousins. Mol. Interv. 2007 Dec; 7(6): 306-9. PMID: 18199851, PII: 7/6/306, DOI: 10.1124/mi.7.6.4, ISSN: 1534-0384.

Mason JN, Deecher DC, Richmond RL, Stack G, Mahaney PE, Trybulski E, Winneker RC, Blakely RD. Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter. J. Pharmacol. Exp. Ther [print-electronic]. 2007 Nov; 323(2): 720-9. PMID: 17673606, PII: jpet.107.125716, DOI: 10.1124/jpet.107.125716, ISSN: 0022-3565.

Williams JM, Owens WA, Turner GH, Saunders C, Dipace C, Blakely RD, France CP, Gore JC, Daws LC, Avison MJ, Galli A. Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine. PLoS Biol. 2007 Oct 10/16/2007; 5(10): e274. PMID: 17941718, PMCID: PMC2020502, PII: 06-PLBI-RA-2396, DOI: 10.1371/journal.pbio.0050274, ISSN: 1545-7885.

Tomlinson ID, Warnerment MR, Mason JN, Vergne MJ, Hercules DM, Blakely RD, Rosenthal SJ. Synthesis and characterization of a pegylated derivative of 3-(1,2,3,6-tetrahydro-pyridin-4yl)-1H-indole (IDT199): a high affinity SERT ligand for conjugation to quantum dots. Bioorg. Med. Chem. Lett [print-electronic]. 2007 Oct 10/15/2007; 17(20): 5656-60. PMID: 17766114, PII: S0960-894X(07)00884-0, DOI: 10.1016/j.bmcl.2007.07.061, ISSN: 0960-894X.

Zhu CB, Steiner JA, Munn JL, Daws LC, Hewlett WA, Blakely RD. Rapid stimulation of presynaptic serotonin transport by A(3) adenosine receptors. J. Pharmacol. Exp. Ther [print-electronic]. 2007 Jul; 322(1): 332-40. PMID: 17460150, PII: jpet.107.121665, DOI: 10.1124/jpet.107.121665, ISSN: 0022-3565.

Bazalakova MH, Wright J, Schneble EJ, McDonald MP, Heilman CJ, Levey AI, Blakely RD. Deficits in acetylcholine homeostasis, receptors and behaviors in choline transporter heterozygous mice. Genes Brain Behav [print-electronic]. 2007 Jul; 6(5): 411-24. PMID: 17010154, PII: GBB269, DOI: 10.1111/j.1601-183X.2006.00269.x, ISSN: 1601-1848.

Blakely RD, DeFelice LJ. All aglow about presynaptic receptor regulation of neurotransmitter transporters. Mol. Pharmacol [print-electronic]. 2007 May; 71(5): 1206-8. PMID: 17329498, PII: mol.107.035493, DOI: 10.1124/mol.107.035493, ISSN: 0026-895X.

Sung U, Blakely RD. Calcium-dependent interactions of the human norepinephrine transporter with syntaxin 1A. Mol. Cell. Neurosci [print-electronic]. 2007 Feb; 34(2): 251-60. PMID: 17188889, PMCID: PMC1847414, PII: S1044-7431(06)00259-4, DOI: 10.1016/j.mcn.2006.11.007, ISSN: 1044-7431.

Wegner AM, McConnell JL, Blakely RD, Wadzinski BE. An automated fluorescence-based method for continuous assay of PP2A activity. Methods Mol. Biol. 2007; 365: 61-9. PMID: 17200554, PII: 1-59745-267-X:61, DOI: 10.1385/1-59745-267-X:61, ISSN: 1064-3745.

Hahn MK, Blakely RD. The functional impact of SLC6 transporter genetic variation. Annu. Rev. Pharmacol. Toxicol. 2007; 47: 401-41. PMID: 17067279, DOI: 10.1146/annurev.pharmtox.47.120505.105242, ISSN: 0362-1642.

Dipace C, Sung U, Binda F, Blakely RD, Galli A. Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent reduction in norepinephrine transporter surface expression linked to changes in syntaxin 1A/transporter complexes. Mol. Pharmacol [print-electronic]. 2007 Jan; 71(1): 230-9. PMID: 17032905, PII: mol.106.026690, DOI: 10.1124/mol.106.026690, ISSN: 0026-895X.

Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology [print-electronic]. 2006 Oct; 31(10): 2121-31. PMID: 16452991, PII: 1301029, DOI: 10.1038/sj.npp.1301029, ISSN: 0893-133X.

Iwamoto H, Blakely RD, De Felice LJ. Na+, Cl-, and pH dependence of the human choline transporter (hCHT) in Xenopus oocytes: the proton inactivation hypothesis of hCHT in synaptic vesicles. J. Neurosci. 2006 Sep 9/27/2006; 26(39): 9851-9. PMID: 17005849, PII: 26/39/9851, DOI: 10.1523/JNEUROSCI.1862-06.2006, ISSN: 1529-2401.

Tomlinson ID, Mason JN, Blakely RD, Rosenthal SJ. High affinity inhibitors of the dopamine transporter (DAT): novel biotinylated ligands for conjugation to quantum dots. Bioorg. Med. Chem. Lett [print-electronic]. 2006 Sep 9/1/2006; 16(17): 4664-7. PMID: 16784853, PII: S0960-894X(06)00644-5, DOI: 10.1016/j.bmcl.2006.05.097, ISSN: 0960-894X.

Carneiro AM, Blakely RD. Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter. J. Biol. Chem [print-electronic]. 2006 Aug 8/25/2006; 281(34): 24769-80. PMID: 16803896, PMCID: PMC3875312, PII: M603877200, DOI: 10.1074/jbc.M603877200, ISSN: 0021-9258.

McDonald PW, Jessen T, Field JR, Blakely RD. Dopamine signaling architecture in Caenorhabditis elegans. Cell. Mol. Neurobiol [print-electronic]. 2006 Jul; 26(4-6): 593-618. PMID: 16724276, DOI: 10.1007/s10571-006-9003-6, ISSN: 0272-4340.

Matthies DS, Fleming PA, Wilkes DM, Blakely RD. The Caenorhabditis elegans choline transporter CHO-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner. J. Neurosci. 2006 Jun 6/7/2006; 26(23): 6200-12. PMID: 16763028, PII: 26/23/6200, DOI: 10.1523/JNEUROSCI.5036-05.2006, ISSN: 1529-2401.

Henry LK, DeFelice LJ, Blakely RD. Getting the message across: a recent transporter structure shows the way. Neuron. 2006 Mar 3/16/2006; 49(6): 791-6. PMID: 16543127, PII: S0896-6273(06)00169-3, DOI: 10.1016/j.neuron.2006.03.002, ISSN: 0896-6273.

Binda F, Lute BJ, Dipace C, Blakely RD, Galli A. The N-terminus of the norepinephrine transporter regulates the magnitude and selectivity of the transporter-associated leak current. Neuropharmacology [print-electronic]. 2006 Mar; 50(3): 354-61. PMID: 16289633, PII: S0028-3908(05)00355-2, DOI: 10.1016/j.neuropharm.2005.09.012, ISSN: 0028-3908.

Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF, Newman AH, Blakely RD. Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J. Biol. Chem [print-electronic]. 2006 Jan 1/27/2006; 281(4): 2012-23. PMID: 16272152, PII: M505055200, DOI: 10.1074/jbc.M505055200, ISSN: 0021-9258.

Bazalakova MH, Blakely RD. The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice. Handb Exp Pharmacol. 2006; (175): 525-44. PMID: 16722248, ISSN: 0171-2004.

Mazei-Robinson MS, Blakely RD. ADHD and the dopamine transporter: are there reasons to pay attention?. Handb Exp Pharmacol. 2006; (175): 373-415. PMID: 16722244, ISSN: 0171-2004.

Keller NR, Diedrich A, Appalsamy M, Miller LC, Caron MG, McDonald MP, Shelton RC, Blakely RD, Robertson D. Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension. Neuroscience [print-electronic]. 2006; 139(3): 931-46. PMID: 16515844, PII: S0306-4522(06)00099-6, DOI: 10.1016/j.neuroscience.2006.01.008, ISSN: 0306-4522.

Tomlinson ID, Mason JN, Blakely RD, Rosenthal SJ. Inhibitors of the serotonin transporter protein (SERT): the design and synthesis of biotinylated derivatives of 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indoles. High-affinity serotonergic ligands for conjugation with quantum dots. Bioorg. Med. Chem. Lett [print-electronic]. 2005 Dec 12/1/2005; 15(23): 5307-10. PMID: 16183285, PII: S0960-894X(05)01060-7, DOI: 10.1016/j.bmcl.2005.08.030, ISSN: 0960-894X.

Mazei-Robison MS, Blakely RD. Expression studies of naturally occurring human dopamine transporter variants identifies a novel state of transporter inactivation associated with Val382Ala. Neuropharmacology [print-electronic]. 2005 Nov; 49(6): 737-49. PMID: 16212992, PII: S0028-3908(05)00317-5, DOI: 10.1016/j.neuropharm.2005.08.012, ISSN: 0028-3908.

Mazei-Robison MS, Couch RS, Shelton RC, Stein MA, Blakely RD. Sequence variation in the human dopamine transporter gene in children with attention deficit hyperactivity disorder. Neuropharmacology [print-electronic]. 2005 Nov; 49(6): 724-36. PMID: 16171832, PII: S0028-3908(05)00307-2, DOI: 10.1016/j.neuropharm.2005.08.003, ISSN: 0028-3908.

Prasad HC, Zhu CB, McCauley JL, Samuvel DJ, Ramamoorthy S, Shelton RC, Hewlett WA, Sutcliffe JS, Blakely RD. Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Aug 8/9/2005; 102(32): 11545-50. PMID: 16055563, PMCID: PMC1183547, PII: 0501432102, DOI: 10.1073/pnas.0501432102, ISSN: 0027-8424.

Sung U, Jennings JL, Link AJ, Blakely RD. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins. Biochem. Biophys. Res. Commun. 2005 Aug 8/5/2005; 333(3): 671-8. PMID: 15963952, PII: S0006-291X(05)01166-6, DOI: 10.1016/j.bbrc.2005.05.165, ISSN: 0006-291X.

Blakely RD, DeFelice LJ, Galli A. Biogenic amine neurotransmitter transporters: just when you thought you knew them. Physiology (Bethesda). 2005 Aug; 20: 225-31. PMID: 16024510, PII: 20/4/225, DOI: 10.1152/physiol.00013.2005, ISSN: 1548-9213.

Sutcliffe JS, Delahanty RJ, Prasad HC, McCauley JL, Han Q, Jiang L, Li C, Folstein SE, Blakely RD. Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am. J. Hum. Genet [print-electronic]. 2005 Aug; 77(2): 265-79. PMID: 15995945, PMCID: PMC1224529, PII: S0002-9297(07)62916-4, DOI: 10.1086/432648, ISSN: 0002-9297.

Nass R, Hahn MK, Jessen T, McDonald PW, Carvelli L, Blakely RD. A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking. J. Neurochem [print-electronic]. 2005 Aug; 94(3): 774-85. PMID: 15992384, PII: JNC3205, DOI: 10.1111/j.1471-4159.2005.03205.x, ISSN: 0022-3042.

Hahn MK, Mazei-Robison MS, Blakely RD. Single nucleotide polymorphisms in the human norepinephrine transporter gene affect expression, trafficking, antidepressant interaction, and protein kinase C regulation. Mol. Pharmacol [print-electronic]. 2005 Aug; 68(2): 457-66. PMID: 15894713, PII: mol.105.011270, DOI: 10.1124/mol.105.011270, ISSN: 0026-895X.

Zhu CB, Carneiro AM, Dostmann WR, Hewlett WA, Blakely RD. P38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process. J. Biol. Chem [print-electronic]. 2005 Apr 4/22/2005; 280(16): 15649-58. PMID: 15728187, PII: M410858200, DOI: 10.1074/jbc.M410858200, ISSN: 0021-9258.

Mason JN, Farmer H, Tomlinson ID, Schwartz JW, Savchenko V, DeFelice LJ, Rosenthal SJ, Blakely RD. Novel fluorescence-based approaches for the study of biogenic amine transporter localization, activity, and regulation. J. Neurosci. Methods [print-electronic]. 2005 Apr 4/15/2005; 143(1): 3-25. PMID: 15763132, PII: S0165-0270(04)00349-8, DOI: 10.1016/j.jneumeth.2004.09.028, ISSN: 0165-0270.

Egli RE, Kash TL, Choo K, Savchenko V, Matthews RT, Blakely RD, Winder DG. Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis. Neuropsychopharmacology. 2005 Apr; 30(4): 657-68. PMID: 15602500, PII: 1300639, DOI: 10.1038/sj.npp.1300639, ISSN: 0893-133X.

Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A. Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Mar 3/1/2005; 102(9): 3495-500. PMID: 15728379, PMCID: PMC549289, PII: 0407737102, DOI: 10.1073/pnas.0407737102, ISSN: 0027-8424.

Tomlinson ID, Mason JN, Blakely RD, Rosenthal SJ. Peptide-conjugated quantum dots: imaging the angiotensin type 1 receptor in living cells. Methods Mol. Biol. 2005; 303: 51-60. PMID: 15923674, PII: 1-59259-901-X:051, DOI: 10.1385/1-59259-901-X:051, ISSN: 1064-3745.

Mason JN, Tomlinson ID, Rosenthal SJ, Blakely RD. Labeling cell-surface proteins via antibody quantum dot streptavidin conjugates. Methods Mol. Biol. 2005; 303: 35-50. PMID: 15923673, PII: 1-59259-901-X:035, DOI: 10.1385/1-59259-901-X:035, ISSN: 1064-3745.

Carvelli L, McDonald PW, Blakely RD, DeFelice LJ. Dopamine transporters depolarize neurons by a channel mechanism. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Nov 11/9/2004; 101(45): 16046-51. PMID: 15520385, PMCID: PMC528740, PII: 0403299101, DOI: 10.1073/pnas.0403299101, ISSN: 0027-8424.

Zhu CB, Hewlett WA, Francis SH, Corbin JD, Blakely RD. Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5 inhibitor sildenafil. Eur. J. Pharmacol. 2004 Nov 11/3/2004; 504(1-2): 1-6. PMID: 15507214, PII: S0014-2999(04)01046-5, DOI: 10.1016/j.ejphar.2004.09.023, ISSN: 0014-2999.

Ferguson SM, Bazalakova M, Savchenko V, Tapia JC, Wright J, Blakely RD. Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Jun 6/8/2004; 101(23): 8762-7. PMID: 15173594, PMCID: PMC423269, PII: 0401667101, DOI: 10.1073/pnas.0401667101, ISSN: 0027-8424.

Zhu CB, Hewlett WA, Feoktistov I, Biaggioni I, Blakely RD. Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation. Mol. Pharmacol. 2004 Jun; 65(6): 1462-74. PMID: 15155839, PII: 65/6/1462, DOI: 10.1124/mol.65.6.1462, ISSN: 0026-895X.

McCauley JL, Olson LM, Dowd M, Amin T, Steele A, Blakely RD, Folstein SE, Haines JL, Sutcliffe JS. Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 May 5/15/2004; 127B(1): 104-12. PMID: 15108191, DOI: 10.1002/ajmg.b.20151, ISSN: 1552-4841.

Ferguson SM, Blakely RD. The choline transporter resurfaces: new roles for synaptic vesicles?. Mol. Interv. 2004 Feb; 4(1): 22-37. PMID: 14993474, PII: 4/1/22, DOI: 10.1124/mi.4.1.22, ISSN: 1543-2548.

Savchenko V, Sung U, Blakely RD. Cell surface trafficking of the antidepressant-sensitive norepinephrine transporter revealed with an ectodomain antibody. Mol. Cell. Neurosci. 2003 Dec; 24(4): 1131-50. PMID: 14697674, PII: S1044743103002355, ISSN: 1044-7431.

Volpicelli-Daley LA, Hrabovska A, Duysen EG, Ferguson SM, Blakely RD, Lockridge O, Levey AI. Altered striatal function and muscarinic cholinergic receptors in acetylcholinesterase knockout mice. Mol. Pharmacol. 2003 Dec; 64(6): 1309-16. PMID: 14645660, PII: 64/6/1309, DOI: 10.1124/mol.64.6.1309, ISSN: 0026-895X.

Ferguson SM, Savchenko V, Apparsundaram S, Zwick M, Wright J, Heilman CJ, Yi H, Levey AI, Blakely RD. Vesicular localization and activity-dependent trafficking of presynaptic choline transporters. J. Neurosci. 2003 Oct 10/29/2003; 23(30): 9697-709. PMID: 14585997, PII: 23/30/9697, ISSN: 1529-2401.

Henry LK, Adkins EM, Han Q, Blakely RD. Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane domain I. J. Biol. Chem [print-electronic]. 2003 Sep 9/26/2003; 278(39): 37052-63. PMID: 12869570, PII: M305514200, DOI: 10.1074/jbc.M305514200, ISSN: 0021-9258.

Hahn MK, Robertson D, Blakely RD. A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters. J. Neurosci. 2003 Jun 6/1/2003; 23(11): 4470-8. PMID: 12805287, PII: 23/11/4470, ISSN: 1529-2401.

Schwartz JW, Blakely RD, DeFelice LJ. Binding and transport in norepinephrine transporters. Real-time, spatially resolved analysis in single cells using a fluorescent substrate. J. Biol. Chem [print-electronic]. 2003 Mar 3/14/2003; 278(11): 9768-77. PMID: 12499385, PII: M209824200, DOI: 10.1074/jbc.M209824200, ISSN: 0021-9258.

Sung U, Apparsundaram S, Galli A, Kahlig KM, Savchenko V, Schroeter S, Quick MW, Blakely RD. A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity. J. Neurosci. 2003 Mar 3/1/2003; 23(5): 1697-709. PMID: 12629174, PII: 23/5/1697, ISSN: 1529-2401.

Nass R, Blakely RD. The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration. Annu. Rev. Pharmacol. Toxicol [print-electronic]. 2003; 43: 521-44. PMID: 12415122, PII: 100901.135934, DOI: 10.1146/annurev.pharmtox.43.100901.135934, ISSN: 0362-1642.

Garland EM, Hahn MK, Ketch TP, Keller NR, Kim CH, Kim KS, Biaggioni I, Shannon JR, Blakely RD, Robertson D. Genetic basis of clinical catecholamine disorders. Ann. N. Y. Acad. Sci. 2002 Oct; 971: 506-14. PMID: 12438171, ISSN: 0077-8923.

Bauman PA, Blakely RD. Determinants within the C-terminus of the human norepinephrine transporter dictate transporter trafficking, stability, and activity. Arch. Biochem. Biophys. 2002 Aug 8/1/2002; 404(1): 80-91. PMID: 12127072, PII: S0003986102002321, ISSN: 0003-9861.

Rosenthal SJ, Tomlinson I, Adkins EM, Schroeter S, Adams S, Swafford L, McBride J, Wang Y, DeFelice LJ, Blakely RD. Targeting cell surface receptors with ligand-conjugated nanocrystals. J. Am. Chem. Soc. 2002 May 5/1/2002; 124(17): 4586-94. PMID: 11971705, PII: ja003486s, ISSN: 0002-7863.

Nass R, Hall DH, Miller DM, Blakely RD. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Mar 3/5/2002; 99(5): 3264-9. PMID: 11867711, PMCID: PMC122507, PII: 042497999, DOI: 10.1073/pnas.042497999, ISSN: 0027-8424.

Hahn MK, Blakely RD. Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders. Pharmacogenomics J. 2002; 2(4): 217-35. PMID: 12196911, DOI: 10.1038/sj.tpj.6500106, ISSN: 1470-269X.

Apparsundaram S, Ferguson SM, Blakely RD. Molecular cloning and characterization of a murine hemicholinium-3-sensitive choline transporter. Biochem. Soc. Trans. 2001 Nov; 29(Pt 6): 711-6. PMID: 11709061, ISSN: 0300-5127.

Blakely RD. Physiological genomics of antidepressant targets: keeping the periphery in mind. J. Neurosci. 2001 Nov 11/1/2001; 21(21): 8319-23. PMID: 11606618, PII: 21/21/8319, ISSN: 1529-2401.

Apparsundaram S, Sung U, Price RD, Blakely RD. Trafficking-dependent and -independent pathways of neurotransmitter transporter regulation differentially involving p38 mitogen-activated protein kinase revealed in studies of insulin modulation of norepinephrine transport in SK-N-SH cells. J. Pharmacol. Exp. Ther. 2001 Nov; 299(2): 666-77. PMID: 11602680, ISSN: 0022-3565.

Blakely RD. Neurobiology. Dopamine's reversal of fortune. Science. 2001 Sep 9/28/2001; 293(5539): 2407-9. PMID: 11577225, PII: 293/5539/2407, DOI: 10.1126/science.1065931, ISSN: 0036-8075.

Nass R, Miller DM, Blakely RD. C. elegans: a novel pharmacogenetic model to study Parkinson's disease. Parkinsonism Relat. Disord. 2001 Jul; 7(3): 185-91. PMID: 11331185, PII: S1353-8020(00)00056-0, ISSN: 1873-5126.

Robertson D, Flattem N, Tellioglu T, Carson R, Garland E, Shannon JR, Jordan J, Jacob G, Blakely RD, Biaggioni I. Familial orthostatic tachycardia due to norepinephrine transporter deficiency. Ann. N. Y. Acad. Sci. 2001 Jun; 940: 527-43. PMID: 11458707, ISSN: 0077-8923.

Adkins EM, Barker EL, Blakely RD. Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition. Mol. Pharmacol. 2001 Mar; 59(3): 514-23. PMID: 11179447, ISSN: 0026-895X.

Bauman AL, Apparsundaram S, Ramamoorthy S, Wadzinski BE, Vaughan RA, Blakely RD. Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. J. Neurosci. 2000 Oct 10/15/2000; 20(20): 7571-8. PMID: 11027216, PII: 20/20/7571, ISSN: 1529-2401.

Apparsundaram S, Ferguson SM, George AL, Blakely RD. Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem. Biophys. Res. Commun. 2000 Oct 10/5/2000; 276(3): 862-7. PMID: 11027560, PII: S0006-291X(00)93561-7, DOI: 10.1006/bbrc.2000.3561, ISSN: 0006-291X.

Blakely RD, Bauman AL. Biogenic amine transporters: regulation in flux. Curr. Opin. Neurobiol. 2000 Jun; 10(3): 328-36. PMID: 10851182, PII: S0959-4388(00)00088-X, ISSN: 0959-4388.

Schroeter S, Apparsundaram S, Wiley RG, Miner LH, Sesack SR, Blakely RD. Immunolocalization of the cocaine- and antidepressant-sensitive l-norepinephrine transporter. J. Comp. Neurol. 2000 May 5/1/2000; 420(2): 211-32. PMID: 10753308, PII: 10.1002/(SICI)1096-9861(20000501)420:2<211::AID-CNE5>3.0.CO;2-3, ISSN: 0021-9967.

Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N. Engl. J. Med. 2000 Feb 2/24/2000; 342(8): 541-9. PMID: 10684912, DOI: 10.1056/NEJM200002243420803, ISSN: 0028-4793.

Flattem NL, Blakely RD. Modified structure of the human serotonin transporter promoter. Mol. Psychiatry. 2000 Jan; 5(1): 110-5. PMID: 10673778, ISSN: 1359-4184.

Ramamoorthy S, Blakely RD. Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science. 1999 Jul 7/30/1999; 285(5428): 763-6. PMID: 10427004, PII: 7686, ISSN: 0036-8075.

Robertson D, Biaggioni I, Ertl AC, Robertson RM, Diedrich A, Blakely RD, Flattem N, Shannon JR. Orthostatic intolerance: emerging genetic and environmental etiologies. J Gravit Physiol. 1999 Jul; 6(1): P51-4. PMID: 11543025, ISSN: 1077-9248.

Barker EL, Moore KR, Rakhshan F, Blakely RD. Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J. Neurosci. 1999 Jun 6/15/1999; 19(12): 4705-17. PMID: 10366604, ISSN: 1529-2401.

Apparsundaram S, Schroeter S, Giovanetti E, Blakely RD. Acute regulation of norepinephrine transport: II. PKC-modulated surface expression of human norepinephrine transporter proteins. J. Pharmacol. Exp. Ther. 1998 Nov; 287(2): 744-51. PMID: 9808705, ISSN: 0022-3565.

Apparsundaram S, Galli A, DeFelice LJ, Hartzell HC, Blakely RD. Acute regulation of norepinephrine transport: I. protein kinase C-linked muscarinic receptors influence transport capacity and transporter density in SK-N-SH cells. J. Pharmacol. Exp. Ther. 1998 Nov; 287(2): 733-43. PMID: 9808704, ISSN: 0022-3565.

Galli A, Blakely RD, DeFelice LJ. Patch-clamp and amperometric recordings from norepinephrine transporters: channel activity and voltage-dependent uptake. Proc. Natl. Acad. Sci. U.S.A. 1998 Oct 10/27/1998; 95(22): 13260-5. PMID: 9789076, PMCID: PMC23775, ISSN: 0027-8424.

Blakely RD, Ramamoorthy S, Schroeter S, Qian Y, Apparsundaram S, Galli A, DeFelice LJ. Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins. Biol. Psychiatry. 1998 Aug 8/1/1998; 44(3): 169-78. PMID: 9693389, PII: S0006-3223(98)00124-3, ISSN: 0006-3223.

Barker EL, Perlman MA, Adkins EM, Houlihan WJ, Pristupa ZB, Niznik HB, Blakely RD. High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol. J. Biol. Chem. 1998 Jul 7/31/1998; 273(31): 19459-68. PMID: 9677366, ISSN: 0021-9258.

Fritz JD, Jayanthi LD, Thoreson MA, Blakely RD. Cloning and chromosomal mapping of the murine norepinephrine transporter. J. Neurochem. 1998 Jun; 70(6): 2241-51. PMID: 9603188, ISSN: 0022-3042.

Ramamoorthy S, Giovanetti E, Qian Y, Blakely RD. Phosphorylation and regulation of antidepressant-sensitive serotonin transporters. J. Biol. Chem. 1998 Jan 1/23/1998; 273(4): 2458-66. PMID: 9442097, ISSN: 0021-9258.

Barker EL, Blakely RD. Structural determinants of neurotransmitter transport using cross-species chimeras: studies on serotonin transporter. Meth. Enzymol. 1998; 296: 475-98. PMID: 9779469, PII: S0076-6879(98)96035-9, ISSN: 0076-6879.

Ramamoorthy S, Melikian HE, Qian Y, Blakely RD. Biosynthesis, N-glycosylation, and surface trafficking of biogenic amine transporter proteins. Meth. Enzymol. 1998; 296: 347-70. PMID: 9779460, PII: S0076-6879(98)96026-8, ISSN: 0076-6879.

Blakely RD, Apparsundaram S. Structural diversity in the catecholamine transporter gene family: molecular cloning and characterization of an L-epinephrine transporter from bullfrog sympathetic ganglia. Adv. Pharmacol. 1998; 42: 206-10. PMID: 9327880, ISSN: 1054-3589.

Justice JB, Danek KS, Kable JW, Barker EL, Blakely RD. Voltammetric approaches to kinetics and mechanism of the norepinephrine transporter. Adv. Pharmacol. 1998; 42: 191-4. PMID: 9327876, ISSN: 1054-3589.

Bradley CC, Blakely RD. Alternative splicing of the human serotonin transporter gene. J. Neurochem. 1997 Oct; 69(4): 1356-67. PMID: 9326263, ISSN: 0022-3042.

Galli A, Petersen CI, deBlaquiere M, Blakely RD, DeFelice LJ. Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel. J. Neurosci. 1997 May 5/15/1997; 17(10): 3401-11. PMID: 9133366, ISSN: 0270-6474.

Apparsundaram S, Moore KR, Malone MD, Hartzell HC, Blakely RD. Molecular cloning and characterization of an L-epinephrine transporter from sympathetic ganglia of the bullfrog, Rana catesbiana. J. Neurosci. 1997 Apr 4/15/1997; 17(8): 2691-702. PMID: 9092590, ISSN: 0270-6474.

Schroeter S, Levey AI, Blakely RD. Polarized expression of the antidepressant-sensitive serotonin transporter in epinephrine-synthesizing chromaffin cells of the rat adrenal gland. Mol. Cell. Neurosci. 1997; 9(3): 170-84. PMID: 9245500, PII: S1044-7431(97)90619-9, DOI: 10.1006/mcne.1997.0619, ISSN: 1044-7431.

Qian Y, Galli A, Ramamoorthy S, Risso S, DeFelice LJ, Blakely RD. Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression. J. Neurosci. 1997 Jan 1/1/1997; 17(1): 45-57. PMID: 8987735, ISSN: 0270-6474.

Schroeter S, Blakely RD. Drug targets in the embryo. Studies on the cocaine- and antidepressant-sensitive serotonin transporter. Ann. N. Y. Acad. Sci. 1996 Oct 10/31/1996; 801: 239-55. PMID: 8959038, ISSN: 0077-8923.

Barker EL, Blakely RD. Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter. Mol. Pharmacol. 1996 Oct; 50(4): 957-65. PMID: 8863842, ISSN: 0026-895X.

Burnette WB, Bailey MD, Kukoyi S, Blakely RD, Trowbridge CG, Justice JB. Human norepinephrine transporter kinetics using rotating disk electrode voltammetry. Anal. Chem. 1996 Sep 9/1/1996; 68(17): 2932-8. PMID: 8794928, ISSN: 0003-2700.

Galli A, Blakely RD, DeFelice LJ. Norepinephrine transporters have channel modes of conduction. Proc. Natl. Acad. Sci. U.S.A. 1996 Aug 8/6/1996; 93(16): 8671-6. PMID: 8710929, PMCID: PMC38731, ISSN: 0027-8424.

Melikian HE, Ramamoorthy S, Tate CG, Blakely RD. Inability to N-glycosylate the human norepinephrine transporter reduces protein stability, surface trafficking, and transport activity but not ligand recognition. Mol. Pharmacol. 1996 Aug; 50(2): 266-76. PMID: 8700133, ISSN: 0026-895X.

DeFelice LJ, Blakely RD. Pore models for transporters?. Biophys. J. 1996 Feb; 70(2): 579-80. PMID: 8789077, PMCID: PMC1224960, PII: S0006-3495(96)79604-2, DOI: 10.1016/S0006-3495(96)79604-2, ISSN: 0006-3495.

Risso S, DeFelice LJ, Blakely RD. Sodium-dependent GABA-induced currents in GAT1-transfected HeLa cells. J. Physiol. (Lond.). 1996 Feb 2/1/1996; 490 ( Pt 3): 691-702. PMID: 8683468, PMCID: PMC1158707, ISSN: 0022-3751.

Saltarelli MD, Bauman AL, Moore KR, Bradley CC, Blakely RD. Expression of the rat brain creatine transporter in situ and in transfected HeLa cells. Dev. Neurosci. 1996; 18(5-6): 524-34. PMID: 8940628, ISSN: 0378-5866.

Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD. Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J. Exp. Biol. 1995 Oct; 198(Pt 10): 2197-212. PMID: 7500004, ISSN: 0022-0949.

Qian Y, Melikian HE, Rye DB, Levey AI, Blakely RD. Identification and characterization of antidepressant-sensitive serotonin transporter proteins using site-specific antibodies. J. Neurosci. 1995 Feb; 15(2): 1261-74. PMID: 7869097, ISSN: 0270-6474.

Barker EL, Kimmel HL, Blakely RD. Chimeric human and rat serotonin transporters reveal domains involved in recognition of transporter ligands. Mol. Pharmacol. 1994 Nov; 46(5): 799-807. PMID: 7969065, ISSN: 0026-895X.

Blakely RD, De Felice LJ, Hartzell HC. Molecular physiology of norepinephrine and serotonin transporters. J. Exp. Biol. 1994 Nov; 196: 263-81. PMID: 7823027, ISSN: 0022-0949.

Moore KR, Blakely RD. Restriction site-independent formation of chimeras from homologous neurotransmitter-transporter cDNAs. BioTechniques. 1994 Jul; 17(1): 130-5, 137. PMID: 7946295, ISSN: 0736-6205.

Melikian HE, McDonald JK, Gu H, Rudnick G, Moore KR, Blakely RD. Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody. J. Biol. Chem. 1994 Apr 4/22/1994; 269(16): 12290-7. PMID: 8163533, ISSN: 0021-9258.

Blakely RD, Moore KR, Qian Y. Tails of serotonin and norepinephrine transporters: deletions and chimeras retain function. Soc. Gen. Physiol. Ser. 1993; 48: 283-300. PMID: 8503051, ISSN: 0094-7733.

Blakely RD, Berson HE. Molecular biology of serotonin receptors and transporters. Clin Neuropharmacol. 1992; 15 Suppl 1 Pt A: 351A-352A. PMID: 1498868, ISSN: 0362-5664.

Blakely RD. Molecular cloning and characterization of neurotransmitter transporters. NIDA Res. Monogr. 1992; 126: 66-83. PMID: 1362795, ISSN: 1046-9516.

Blakely RD, Berson HE, Fremeau RT, Caron MG, Peek MM, Prince HK, Bradley CC. Cloning and expression of a functional serotonin transporter from rat brain. Nature. 1991 Nov 11/7/1991; 354(6348): 66-70. PMID: 1944572, DOI: 10.1038/354066a0, ISSN: 0028-0836.

Blakely RD, Clark JA, Rudnick G, Amara SG. Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters. Anal. Biochem. 1991 May 5/1/1991; 194(2): 302-8. PMID: 1862934, ISSN: 0003-2697.

Pacholczyk T, Blakely RD, Amara SG. Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 3/28/1991; 350(6316): 350-4. PMID: 2008212, DOI: 10.1038/350350a0, ISSN: 0028-0836.

Pacholczyk T, Blakely RD, Amara SG. A device to rapidly core out tissue culture plates for autoradiographic visualization of cells transfected with cDNA libraries. BioTechniques. 1990 Nov; 9(5): 556-8. PMID: 2268421, ISSN: 0736-6205.

Blakely RD, Robinson MB, Amara SG. Expression of neurotransmitter transport from rat brain mRNA in Xenopus laevis oocytes. Proc. Natl. Acad. Sci. U.S.A. 1988 Dec; 85(24): 9846-50. PMID: 2904681, PMCID: PMC282878, ISSN: 0027-8424.

Blakely RD, Coyle JT. The neurobiology of N-acetylaspartylglutamate. Int. Rev. Neurobiol. 1988; 30: 39-100. PMID: 3061970, ISSN: 0074-7742.