Synapsin is a novel Rab3 effector protein on small synaptic vesicles

II. Functional effects of the Rab3A-synapsin I interaction

Silvia Giovedì, François Darchen, Flavia Valtorta, Paul Greengard, Fabio Benfenati

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Synapsins, a family of neuron-specific phosphoproteins that play an important role in the regulation of synaptic vesicle trafficking and neurotransmitter release, were recently demonstrated to interact with the synaptic vesicle-associated small G protein Rab3A within nerve terminals (Giovedì, S., Vaccaro, P., Valtorta, F., Darchen, F., Greengard, P., Cesareni, G., and Benfenati, F. (2004) J. Biol. Chem. 279, 43760-43768). We have analyzed the functional consequences of this interaction on the biological activities of both proteins and on their subcellular distribution within nerve terminals. The presence of synapsin I stimulated GTP binding and GTPase activity of both purified and endogenous synaptic vesicle-associated Rab3A. Conversely, Rab3A inhibited synapsin I binding to F-actin, as well as synapsin-induced actin bundling and vesicle clustering. Moreover, the amount of Rab3A associated with synaptic vesicles was decreased in synapsin knockout mice, and the presence of synapsin I prevented RabGDI-induced Rab3A dissociation from synaptic vesicles. The results indicate that an interaction between synapsin I and Rab3A exists on synaptic vesicles that modulates the functional properties of both proteins. Given the well recognized importance of both synapsins and Rab3A in synaptic vesicles exocytosis, this interaction is likely to play a major role in the modulation of neurotransmitter release.

Original languageEnglish
Pages (from-to)43769-43779
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number42
DOIs
Publication statusPublished - Oct 15 2004

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rab3 GTP-Binding Proteins
Synapsins
Synaptic Vesicles
Proteins
Neurotransmitter Agents
Actins
Monomeric GTP-Binding Proteins
GTP Phosphohydrolases
Phosphoproteins
Exocytosis
Guanosine Triphosphate
Bioactivity
Knockout Mice
Neurons
Cluster Analysis
Modulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Synapsin is a novel Rab3 effector protein on small synaptic vesicles : II. Functional effects of the Rab3A-synapsin I interaction. / Giovedì, Silvia; Darchen, François; Valtorta, Flavia; Greengard, Paul; Benfenati, Fabio.

In: Journal of Biological Chemistry, Vol. 279, No. 42, 15.10.2004, p. 43769-43779.

Research output: Contribution to journalArticle

Giovedì, Silvia ; Darchen, François ; Valtorta, Flavia ; Greengard, Paul ; Benfenati, Fabio. / Synapsin is a novel Rab3 effector protein on small synaptic vesicles : II. Functional effects of the Rab3A-synapsin I interaction. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 42. pp. 43769-43779.
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