TY - JOUR T1 - The Phospho-Dependent Dynamin–Syndapin Interaction Triggers Activity-Dependent Bulk Endocytosis of Synaptic Vesicles JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7706 LP - 7717 DO - 10.1523/JNEUROSCI.1976-09.2009 VL - 29 IS - 24 AU - Emma L. Clayton AU - Victor Anggono AU - Karen J. Smillie AU - Ngoc Chau AU - Phillip J. Robinson AU - Michael A. Cousin Y1 - 2009/06/17 UR - http://www.jneurosci.org/content/29/24/7706.abstract N2 - 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. ER -