Attenuation of the norepinephrine transporter activity and trafficking via interactions with α-synuclein

European Journal of Neuroscience

Volumn 24, Issue 11, 2006, Pages 3141-3152

  Wersinger, Christophe ^a   Jeannotte, Alexis ^a   Sidhu, Anita ^a,b  

^a GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b GEORGETOWN UNIVERSITY   (United States)

Author keywords

synuclein; Depression; Norepinephrine transporter; Parkinson's disease; Protein : protein interactions; Trafficking

Indexed keywords

ALPHA SYNUCLEIN; DNA; NISOXETINE; NORADRENALIN; NORADRENALIN TRANSPORTER; TRITIUM;

ARTICLE; BIOTINYLATION; CELL SURFACE; CONTROLLED STUDY; EMBRYO; GENETIC TRANSFECTION; HOMEOSTASIS; HUMAN; HUMAN CELL; NERVE CELL; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION;

ALPHA-SYNUCLEIN; ANIMALS; BRAIN; CELL LINE; HOMEOSTASIS; HUMANS; MALE; NEURONS; NOREPINEPHRINE; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; RATS; RATS, SPRAGUE-DAWLEY; SYMPATHETIC NERVOUS SYSTEM; SYNAPSES; SYNAPTIC TRANSMISSION; TRANSFECTION;

EID: 33845605950     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/j.1460-9568.2006.05181.x     Document Type: Article

References (67)

1. Amaral, D.G. & Sinnamon, H.M. (1977) The locus coeruleus: neurobiology of a central noradrenergic nucleus. Prog. Neurobiol., 9, 147-196.
2. Apparsundaram, S., Galli, A., DeFelice, L.J., Hartzell, H.C. & Blakely, R.D. (1998a) 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., 287, 733-743.
3. Apparsundaram, S., Schroeter, S., Giovanetti, E. & Blakely, R.D. (1998b) Acute regulation of norepinephrine transport. II. PKC-modulated surface expression of human norepinephrine transporter proteins. J. Pharmacol. Exp. Ther., 287, 744-751.
4. Apparsundaram, S., Sung, U., Price, R.D. & Blakely, R.D. (2001) 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., 299, 666-677.
5. Aston-Jones, G. & Cohen, J.D. (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu. Rev. Neurosci., 28, 403-450.
6. Aston-Jones, G. & Harris, G.C. (2004) Brain substrates for increased drug seeking during protracted withdrawal. Neuropharmacology, 47 (Suppl. 1), 167-179.
7. Aston-Jones, G., Rajkowski, J. & Cohen, J. (2000) Locus coeruleus and regulation of behavioral flexibility and attention. Prog. Brain Res., 126, 165-182.
8. Bauman, A.L., Apparsundaram, S., Ramamoorthy, S., Wadzinski, B.E., Vaughan, R.A. & Blakely, R.D. (2000) Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. J. Neurosci., 20, 7571-7578.
9. Bennett, M.C. (2005) The role of alpha-synuclein in neurodegenerative diseases. Pharmacol. Ther., 105, 311-331.
10. Bonini, N.M. & Giasson, B.I. (2005) Snaring the function of alpha-synuclein. Cell, 123, 359-361.
11. Braak, E., Sandmann-Keil, D., Rub, U., Gai, W.P., de Vos, R.A., Steur, E.N., Arai, K. & Braak, H. (2001) Alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei. Acta Neuropathol. (Berl.), 101, 195-201.
12. Brenz Verca, M.S., Bahi, A., Boyer, F., Wagner, G.C. & Dreyer, J.L. (2003) Distribution of alpha- and gamma-synucleins in the adult rat brain and their modification by high-dose cocaine treatment. Eur. J. Neurosci., 18, 1923-1938.
13. Brown, R.T., Amler, R.W., Freeman, W.S., Perrin, J.M., Stein, M.T., Feldman, H.M., Pierce, K. & Wolraich, M.L. (2005) Treatment of attention-deficit/hyperactivity disorder: overview of the evidence. Pediatrics, 5, e749-757.
14. Cabin, D.E., Shimazu, K., Murphy, D., Cole, N.B., Gottschalk, W., McIlwain, K.L., Orrison, B., Chen, A., Ellis, C.E., Paylor, R., Lu, B. & Nussbaum, R.L. (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J. Neurosci., 22, 8797-8807.
15. Carboni, E. & Silvagni, A. (2004) Dopamine reuptake by norepinephrine neurons: exception or rule? Crit. Rev. Neurobiol., 16, 121-128.
16. Carneiro, A.M., Ingram, S.L., Beaulieu, J.M., Sweeney, A., Amara, S.G., Thomas, S.M., Caron, M.G. & Torres, G.E. (2002) The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter. J. Neurosci., 22, 7045-7054.
17. Chandra, S., Gallardo, G., Fernandez-Chacon, R., Schluter, O.M. & Sudhof, T.C. (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell, 123, 383-396.
18. Clayton, D.F. & George, J.M. (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci., 21, 249-254.
19. Corman, S.L., Fedutes, B.A. & Culley, C.M. (2004) Atomoxetine: the first nonstimulant for the management of attention-deficit/hyperactivity disorder. Am. J. Health Syst. Pharm., 61, 2391-2399.
20. Fortin, D.L., Troyer, M.D., Nakamura, K., Kubo, S., Anthony, M.D. & Edwards, R.H. (2004) Lipid rafts mediate the synaptic localization of alpha-synuclein. J. Neurosci., 24, 6715-6723.
21. George, J.M. (2002) The synucleins. Genome Biol., 3, 1-6.
22. Gesi, M., Soldani, P., Giorgi, F.S., Santinami, A., Bonaccorsi, I. & Fornai, F. (2000) The role of the locus coeruleus in the development of Parkinson's disease. Neurosci. Biobehav. Rev., 24, 655-668.
23. Hoffman, B.J., Hansson, S.R., Mezey, E. & Palkovits, M. (1998) Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system. Front. Neuroendocrinol., 19, 187-231.
24. Jayanthi, L.D., Samuvel, D.J. & Ramamoorthy, S. (2004) Regulated internalization and phosphorylation of the native norepinephrine transporter in response to phorbol esters. Evidence for localization in lipid rafts and lipid raft-mediated internalization. J. Biol. Chem., 279, 19315-19326.
25. Jellinger, K.A. (1991) Pathology of Parkinson's disease. Changes other than the nigrostriatal pathway. Mol. Chem. Neuropathol., 14, 153-197.
26. Jellinger, K.A. (2000) Morphological substrates of mental dysfunction in Lewy body disease: an update. J. Neural. Transm. Suppl., 59, 185-212.
27. Jensen, P.H., Nielsen, M.S., Jakes, R., Dotti, C.G. & Goedert, M. (1998) Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation. J. Biol. Chem., 273, 26292-26294.
28. Kaminski, R.M., Shippenberg, T.S., Witkin, J.M. & Rocha, B.A. (2005) Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures. Neurosci. Lett., 382, 51-55.
29. Klimek, V., Stockmeier, C., Overholser, J., Meltzer, H.Y., Kalka, S., Dilley, G. & Ordway, G.A. (1997) Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J. Neurosci., 17, 8451-8458.
30. Kubo, S., Nemani, V.M., Chalkley, R.J., Anthony, M.D., Hattori, N., Mizuno, Y., Edwards, R.H. & Fortin, D.L. (2005) A combinatorial code for the interaction of alpha-synuclein with membranes. J. Biol. Chem., 280, 31664-31672.
31. Li, J.Y., Henning Jensen, P. & Dahlstrom, A. (2002) Differential localization of alpha-, beta- and gamma-synucleins in the rat CNS. Neuroscience, 113, 463-478.
32. Lotharius, J. & Brundin, P. (2002a) Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum. Mol. Genet., 11, 2395-2407.
33. Lotharius, J. & Brundin, P. (2002b) Pathogenesis of Parkinson's disease: dopamine, vesicles, and alpha-synuclein. Nat. Rev. Neurosci., 3, 932-942.
34. Mandela, P. & Ordway, G.A. (2006) The norepinephrine transporter and its regulation. J. Neurochem., March 15 [Epub ahead of print].
35. Marien, M.R., Colpaert, F.C. & Rosenquist, A.C. (2004) Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res. Brain Res. Rev., 45, 38-78.
36. Maries, E., Dass, B., Collier, T.J., Kordower, J.H. & Steece-Collier, K. (2003) The role of alpha-synuclein in Parkinson's disease: insights from animal models. Nat. Rev. Neurosci., 4, 727-738.
37. Mash, D.C., Ouyang, Q., Pablo, J., Basile, M., Izenwasser, S., Lieberman, A. & Perrin, R.J. (2003) Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons. J. Neurosci., 23, 2564-2571.
38. Mead, A.N., Rocha, B.A., Donovan, D.M. & Katz, J.L. (2002) Intravenous cocaine induced-activity and behavioural sensitization in norepinephrine-, but not dopamine-transporter knockout mice. Eur. J. Neurosci., 16, 514-520.
39. Melikian, H.E., McDonald, J.K., Gu, H., Rudnick, G., Moore, K.R. & Blakely, R.D. (1994) Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody. J. Biol. Chem., 269, 12290-12297.
40. Miner, L.H., Schroeter, S., Blakely, R.D. & Sesack, S.R. (2003) Ultrastructural localization of the norepinephrine transporter in superficial and deep layers of the rat prelimbic prefrontal cortex and its spatial relationship to probable dopamine terminals. J. Comp. Neurol., 466, 478-494.
41. Moron, J.A., Brockington, A., Wise, R.A., Rocha, B.A. & Hope, B.T. (2002) Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J. Neurosci., 22, 389-395.
42. Nelson, N. (1998) The family of Na+/Cl- neurotransmitter transporters. J. Neurochem., 71, 1785-1803.
43. Ostrerova, N., Petrucelli, L., Farrer, M., Mehta, N., Choi, P., Hardy, J. & Wolozin, B. (1999) alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J. Neurosci., 19, 5782-5791.
44. Pacholczyk, T., Blakely, R.D. & Amara, S.G. (1991) Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature, 350, 350-354.
45. Pan, W.H., Yang, S.Y. & Lin, S.K. (2004) Neurochemical interaction between dopaminergic and noradrenergic neurons in the medial prefrontal cortex. Synapse, 53, 44-52.
46. Ramamoorthy, S., Melikian, H.E., Qian, Y. & Blakely, R.D. (1998) Biosynthesis, N-glycosylation, and surface trafficking of biogenic amine transporter proteins. Meth. Enzymol., 296, 347-370.
47. Ressler, K.J. & Nemeroff, C.B. (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress. Anxiety, 12, 2-19.
48. Schroeter, S., Apparsundaram, S., Wiley, R.G., Miner, L.H., Sesack, S.R. & Blakely, R.D. (2000) Immunolocalization of the cocaine- and antidepressant-sensitive 1-norepinephrine transporter. J. Comp. Neurol., 420, 211-232.
49. Sidhu, A., Wersinger, C. & Vernier, P. (2004a) Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse? FASEB J., 18, 637-647.
50. Sidhu, A., Wersinger, C. & Vernier, P. (2004b) Alpha-synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease. FEBS Lett., 565, 1-5.
51. Smythies, J. (2005) Section III. The norepinephrine system. Int. Rev. Neurobiol., 64, 173-211.
52. Sung, U., Apparsundaram, S., Galli, A., Kahlig, K.M., Savchenko, V., Schroeter, S., Quick, M.W. & Blakely, R.D. (2003) A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity. J. Neurosci., 23, 1697-1709.
53. Sung, U., Jennings, J.L., Link, A.J. & Blakely, R.D. (2005) Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins. Biochem. Biophys. Res. Commun., 333, 671-678.
54. Torres, G.E., Gainetdinov, R.R. & Caron, M.G. (2003) Plasma membrane monoamine transporters: structure, regulation and function. Nat. Rev. Neurosci., 4, 13-25.
55. Torres, G.E., Yao, W.D., Mohn, A.R., Quan, H., Kim, K.M., Levey, A.I., Staudinger, J. & Caron, M.G. (2001) Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron, 30, 121-134.
56. Uchida, J., Kiuchi, Y., Ohno, M., Yura, A., Oguchi, K. (1998) Ca(2+)-dependent enhancement of [3H]noradrenaline uptake in PC12 cells through calmodulin-dependent kinases. Brain Res., 809, 155-164. (2002)
57. Vermetten, E. & Bremner, J.D. (2002) Circuits and systems in stress. I. Preclinical studies. Depress. Anxiety, 15, 126-147.
58. Vizi, E.S., Zsilla, G., Caron, M.G. & Kiss, J.P. (2004) Uptake and release of norepinephrine by serotonergic terminals in norepinephrine transporter knock-out mice: implications for the action of selective serotonin reuptake inhibitors. J. Neurosci., 24, 7888-7894.
59. Wersinger, C., Banta, M. & Sidhu, A. (2004a) Comparative analyses of alpha-synuclein expression levels in rat brain tissues and transfected cells. Neurosci. Lett., 358, 95-98.
60. Wersinger, C., Vernier, P. & Sidhu, A. (2004b) Trypsin disrupts the trafficking of the human dopamine transporter by alpha-synuclein and its A30P mutant. Biochemistry, 43, 1242-1253.
61. Wersinger, C., Prou, D., Vernier, P. & Sidhu, A. (2003a) Modulation of dopamine transporter function by alpha-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. FASEB J., 17, 2151-2153.
62. Wersinger, C., Prou, D., Vernier, P., Niznik, H.B. & Sidhu, A. (2003b) Mutations in the lipid-binding domain of α-synuclein confer overlapping, yet distinct, functional properties in the regulation of dopamine transporter activity. Mol. Cell. Neurosci., 24, 91-105.
63. Wersinger, C., Rusnak, M. & Sidhu, A. (2006) Modulation of the trafficking of human serotonin by human alpha-synuclein. Eur. J. Neurosci., 24, 55-64.
64. Wersinger, C. & Sidhu, A. (2003) Attenuation of dopamine transporter activity by alpha-synuclein. Neurosci. Lett., 340, 189-192.
65. Wersinger, C. & Sidhu, A. (2005) Disruption of the interaction of α-synuclein with microtubules enhances cell surface recruitment of the dopamine transporter. Biochemistry, 44, 13612-13624.
66. Yang, H. & Raizada, M.K. (1999) Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat. J. Neurosci., 19, 2413-2423.
67. - dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol. Ther., 92, 21-55.