The Phospho-Dependent Dynamin-Syndapin Interaction Triggers Activity-Dependent Bulk Endocytosis of Synaptic Vesicles

E. L. Clayton, V. Anggono, K. J. Smillie, N. Chau, P. J. Robinson, M. A. Cousin

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptic vesicles (SVs) are retrieved by more than one mode in central nerve terminals. During mild stimulation, the dominant SV retrieval pathway is classical clathrin-mediated endocytosis (CME). During elevated neuronal activity, activity-dependent bulk endocytosis (ADBE) predominates, which requires activation of the calcium-dependent protein phosphatase calcineurin. We now report that calcineurin dephosphorylates dynamin I in nerve terminals only above the same activity threshold that triggers ADBE. ADBE was arrested when the two major phospho-sites on dynamin I were perturbed, suggesting that dynamin I dephosphorylation is a key step in its activation. Dynamin I dephosphorylation stimulates a specific dynamin I-syndapin I interaction. Inhibition of this interaction by competitive peptides or by site-directed mutagenesis exclusively inhibited ADBE but did not affect CME. The results reveal that the phospho-dependent dynamin-syndapin interaction recruits ADBE to massively increase SV endocytosis under conditions of elevated neuronal activity.
Original languageEnglish
Pages (from-to)7706-7717
Number of pages12
JournalJournal of Neuroscience
Volume29
Issue number24
DOIs
Publication statusPublished - Jun 2009

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