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Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals

Jovanovic, JN; Sihra, TS; Nairn, AC; Hemmings, HC; Greengard, P; Czernik, AJ; (2001) Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals. J NEUROSCI , 21 (20) 7944 - 7953. Green open access

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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.

Type: Article
Title: Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals
Open access status: An open access version is available from UCL Discovery
Publisher version: http://www.jneurosci.org/content/21/20/7944.full
Language: English
Additional information: This work is available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.
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, DEPENDENT PROTEIN-KINASE, SMALL SYNAPTIC VESICLES, RABBIT SKELETAL-MUSCLE, NEUROTRANSMITTER RELEASE, CYCLIC-AMP, NEUROMUSCULAR-JUNCTION, CATALYTIC SUBUNIT, MAMMALIAN BRAIN, PHOSPHATASE 2A, RAT FOREBRAIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/125706
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