Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions

Jovanovic, J.N., Benfenati, F., Siow, Y.L., Sihra, T.S., Sanghera, J.S., Pelech, S.L., Greengard, P. and Czernik, A.J. (1996) Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions. Proceedings of the National Academy of Sciences of the United States of America, 93 (8). pp. 3679-3683.

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Official URL: http://www.pnas.org/content/93/8/3679.full.pdf

Abstract

The ability of neurotrophins to modulate the survival and differentiation of neuronal populations involves the Trk/MAP (mitogen-activated protein kinase) kinase signaling pathway, More recently, neurotrophins have also been shown to regulate synaptic transmission, The synapsins are a family of neuron-specific phosphoproteins that play a role in regulation of neurotransmitter release, in axonal elongation, and in formation and maintenance of synaptic contacts, We report here that synapsin I is a downstream effector for the neurotrophin/Trk/MAP kinase cascade, Using purified components, we show that MAP kinase stoichiometrically phosphorylated synapsin I at three sites (Ser-62, Ser-67, and Ser-549). Phosphorylation of these sites was detected in rat brain homogenates, in cultured cerebrocortical neurons, and in isolated presynaptic terminals, Brain-derived neurotrophic factor and nerve growth factor upregulated phosphorylation of synapsin I at MAP kinase-dependent sites in intact cerebrocortical neurons and PC12 cells, respectively, while KCI-induced depolarization of cultured neurons decreased the phosphorylation state at these sites, MAP kinase-dependent phosphorylation of synapsin I significantly reduced its ability to promote G-actin polymerization and to bundle actin filaments, The results suggest that MAP kinase-dependent phosphorylation of synapsin I may contribute to the modulation of synaptic plasticity by neurotrophins and by other signaling pathways that converge at the level of MAP kinase activation.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2030
Journal or Publication Title:Proceedings of the National Academy of Sciences of the United States of America
Deposited By:Library Staff
Deposited On:07 Apr 2011 14:09
Last Modified:07 Apr 2011 14:09

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