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

E. L. Clayton, N. Sue, K. J. Smillie, T. O'Leary, N. Bache, G. Cheung, A. R. Cole, D. J. Wyllie, C. Sutherland, P. J. Robinson, M. A. Cousin

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)845-851
Number of pages7
JournalNature Neuroscience
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 2010

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