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Titolo:
Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A
Autore:
Bauman, AL; Apparsundaram, S; Ramamoorthy, S; Wadzinski, BE; Vaughan, RA; Blakely, RD;
Indirizzi:
Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58202 USA Univ N Dakota Grand Forks ND USA 58202 ol Biol, Grand Forks, ND 58202 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 20, volume: 20, anno: 2000,
pagine: 7571 - 7578
SICI:
0270-6474(20001015)20:20<7571:CAABAT>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; HUMAN NOREPINEPHRINE TRANSPORTER; CELL-SURFACE EXPRESSION; SEROTONIN TRANSPORTER; KINASE-C; FUNCTIONAL REGULATION; SIGNALING COMPLEX; DORSAL STRIATUM; DEFICIENT MICE; PHORBOL ESTERS;
Keywords:
serotonin; norepinephrine; dopamine; transporter; protein phosphatase 2A; protein kinase C; phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Blakely, RD Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Sch Med, 417 MRBII, Nashville,TN 37232 USA Vanderbilt Univ 417 MRBII Nashville TN USA 37232 ,TN 37232 USA
Citazione:
A.L. Bauman et al., "Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A", J NEUROSC, 20(20), 2000, pp. 7571-7578

Abstract

Presynaptic transporter proteins regulate the clearance of extracellular biogenic amines after release and are important targets for multiple psychoactive agents, including amphetamines, cocaine, and antidepressant drugs. Recent studies reveal that dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters (DAT, NET, and SERT, respectively) are rapidly regulated by direct or receptor-mediated activation of cellular kinases, particularly protein kinase C (PKC). With SERTs, PKC activation results in activity-dependent transporter phosphorylation and sequestration. Protein phosphatase1/2A (PP1/PP2A) inhibitors, such as okadaic acid (OA) and calyculin A, also promote SERT phosphorylation and functional downregulation. How kinase, phosphatase, and transporter activities are linked mechanistically is unclear. In the present study, we found that okadaic acid-sensitive phosphatase activity is enriched in SERT immunoprecipitates from human SERT stably transfected cells. Moreover, blots of these immunoprecipitates reveal the presence of PP2A catalytic subunit (PP2Ac), findings replicated using brain preparations. Whole-cell treatments with okadaic acid or calyculin A diminished SERT/PP2Ac associations. Phorbol esters, which trigger SERT phosphorylation, also diminish SERT/PP2Ac associations, effects that can be blocked by PKCantagonists as well as the SERT substrate 5-HT. Similar transporter/PP2Ac complexes were also observed in coimmunoprecipitation studies with NETs andDATs. Our findings provide evidence for the existence of regulated heteromeric assemblies involving biogenic amine transporters and PP2A and suggest that the dynamic stability of these complexes may govern transporter phosphorylation and sequestration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 18:57:39