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PMID: 20526333 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.

Nature neuroscience ·Vol. 13 ·No. 7 ·2010-07-00 ·Pages 845-51

Clayton EL, Sue N, Smillie KJ, O'Leary T, Bache N, Cheung G, Cole AR, Wyllie DJ, Sutherland C, Robinson PJ, Cousin MA

Abstract

Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity.

MeSH Terms
Animals Cells, Cultured Cerebellum/cytology,metabolism Cyclin-Dependent Kinase 5/metabolism Dynamin I/metabolism Endocytosis/physiology Glycogen Synthase Kinase 3/metabolism Hippocampus/cytology,metabolism In Vitro Techniques Male Neurons/cytology,metabolism Phosphorylation/physiology Presynaptic Terminals/metabolism Rats Rats, Sprague-Dawley Signal Transduction/physiology Synaptic Vesicles/metabolism
Chemicals
Cyclin-Dependent Kinase 5 Glycogen Synthase Kinase 3 Dynamin I
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Clayton Emma L
Centre for Integrative Physiology, George Square, University of Edinburgh, Edinburgh, Scotland, UK.
Sue Nancy
Smillie Karen J
O'Leary Timothy
Bache Nicolai
Cheung Giselle
Cole Adam R
Wyllie David J
Sutherland Calum
Robinson Phillip J
Cousin Michael A
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2571
Published
2010-07-00
Epub
2010-00-06
Pages
845-51
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2894011
Subset
IM
Grants
Wellcome Trust · 070569 · United Kingdom
Wellcome Trust · 084277 · United Kingdom
Biotechnology and Biological Sciences Research Council · C18727 · United Kingdom
Medical Research Council · 88158 · United Kingdom
External Links
PubMed source DOI: 10.1038/nn.2571 PMC Full Text View journal details
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