Opposing Changes in Phosphorylation of Specific Sites in Synapsin I During Ca2-Dependent Glutamate Release in Isolated Nerve Terminals

Jovanovic, J.N., Sihra, T.S., Nairn, A.C., Hemmings, H.C., Greengard, P. and Czernik, A.J. (2001) Opposing Changes in Phosphorylation of Specific Sites in Synapsin I During Ca2-Dependent Glutamate Release in Isolated Nerve Terminals. Journal of Neuroscience, 21 (20). pp. 7944-7963.

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Abstract

Synapsins are major neuronal phosphoproteins involved in regulation of neurotransmitter release. Synapsins are well established targets for multiple protein kinases within the nerve terminal, yet little is known about dephosphorylation processes involved in regulation of synapsin function. Here, we observed a reciprocal relationship in the phosphorylation–dephosphorylation of the established phosphorylation sites on synapsin I. We demonstrate that, in vitro, phosphorylation sites 1, 2, and 3 of synapsin I (P-site 1 phosphorylated by cAMP-dependent protein kinase; P-sites 2 and 3 phosphorylated by Ca2– calmodulin-dependent protein kinase II) were excellent substrates for protein phosphatase 2A, whereas P-sites 4, 5, and 6 (phosphorylated by mitogen-activated protein kinase) were efficiently dephosphorylated only by Ca2–calmodulin-dependent protein phosphatase 2B–calcineurin. In isolated nerve terminals, rapid changes in synapsin I phosphorylation were observed after Ca2 entry, namely, a Ca2-dependent phosphorylation of P-sites 1, 2, and 3 and a Ca2-dependent dephosphorylation of P-sites 4, 5, and 6. Inhibition of calcineurin activity by cyclosporin A resulted in a complete block of Ca2-dependent dephosphorylation of P-sites 4, 5, and 6 and correlated with a prominent increase in ionomycin-evoked glutamate release. These two opposing, rapid, Ca2-dependent processes may play a crucial role in the modulation of synaptic vesicle trafficking within the presynaptic terminal.

Item Type:Article
Uncontrolled Keywords:4-aminopyridine; brain-derived neurotrophic factor (BDNF); Ca2; calcineurin; cyclosporin A; glutamate; ionomycin; mitogen-activated protein (MAP) kinase; neurotrophins; okadaic acid; PD98059; phosphatases; synapsins; synaptosomes; neurotransmitter release
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2023
Journal or Publication Title:Journal of Neuroscience
Deposited By:Library Staff
Deposited On:07 Apr 2011 11:49
Last Modified:07 Apr 2011 11:49

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