Persistence of quantal synaptic vesicle recycling in virtual absence of dynamins

Author:

Afuwape Olusoji A. T.1,Chanaday Natali L.2ORCID,Kasap Merve3,Monteggia Lisa M.45,Kavalali Ege T.45ORCID

Affiliation:

1. Department of Neurosurgery University of Arkansas for Medical Sciences Little Rock Arkansas USA

2. Department of Physiology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

3. U.S. Food and Drug Administration The Center for Drug Evaluation and Research (CDER) Silver Spring Maryland USA

4. Department of Pharmacology Vanderbilt University Nashville Tennessee USA

5. Vanderbilt Brain Institute Vanderbilt University Nashville Tennessee USA

Abstract

AbstractDynamins are GTPases required for pinching vesicles off the plasma membrane once a critical curvature is reached during endocytosis. Here, we probed dynamin function in central synapses by depleting all three dynamin isoforms in postnatal hippocampal neurons down to negligible levels. We found a decrease in the propensity of evoked neurotransmission as well as a reduction in synaptic vesicle numbers. Recycling of synaptic vesicles during spontaneous or low levels of evoked activity were largely impervious to dynamin depletion, while retrieval of synaptic vesicle components at higher levels of activity was partially arrested. These results suggest the existence of balancing dynamin‐independent mechanisms for synaptic vesicle recycling at central synapses. Classical dynamin‐dependent mechanisms are not essential for retrieval of synaptic vesicle proteins after quantal single synaptic vesicle fusion, but they become more relevant for membrane retrieval during intense, sustained neuronal activity. imageKey points Loss of dynamin 2 does not impair synaptic transmission. Loss of all three dynamin isoforms mostly affects evoked neurotransmission. Excitatory synapse function is more susceptible to dynamin loss. Spontaneous neurotransmission is only mildly affected by loss of dynamins. Single synaptic vesicle endocytosis is largely dynamin independent.

Publisher

Wiley

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