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J Biol Chem. 2009 Jan 16;284(3):1930-7. doi: 10.1074/jbc.M803691200. Epub 2008 Nov 14.

Dynamin and activity regulate synaptic vesicle recycling in sympathetic neurons.

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Department of Neurobiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.


Neurotransmission in central neuronal synapses is supported by the recycling of synaptic vesicles via endocytosis at different time scales during and after transmitter release. Here, we examine the kinetics and molecular determinants of different modes of synaptic vesicle recycling at a peripheral neuronal synapse formed between superior cervical ganglion neurons in culture, via acute disruption of endocytosis with Dynasore, an inhibitor of dynamin activation, or a dynamin peptide (P4) that perturbs linkage of dynamin to clathrin coats through amphiphysin. When paired action potentials are generated to produce excitatory postsynaptic potential responses, the second response was reduced after application of Dynasore but not P4. In addition, graded reduction in synaptic transmission during a train of action potentials was accelerated by Dynasore but enhanced by P4. After full depletion of releasable vesicles, P4 delayed the recovery of synaptic transmission while Dynasore limited recovery to 10%. In control neurons, synaptic transmission is stable for more than 1 h under low frequency presynaptic stimulation (0.2 Hz), but was reduced gradually by P4 and rapidly but incompletely blocked by Dynasore at a much lower stimulation frequency. These results suggest two essential modes of dynamin-mediated synaptic vesicle recycling, one activity-dependent and the other activity-independent. Our findings extend the current understanding of synaptic vesicle recycling to sympathetic nerve terminals and provide evidence for a physiological and molecular heterogeneity in endocytosis, a key cellular process for efficient replenishment of the vesicle pool, and thus for synaptic plasticity.

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