UC San Diego

Neurons express three closely related dynamin genes. Dynamin 1 has long been implicated in the regulation of synaptic vesicle recycling in nerve terminals, and dynamins 2 and 3 were more recently shown also to contribute to synaptic vesicle recycling in specific and distinguishable ways. In cultured hippocampal neurons we found that chronic suppression of spontaneous network activity differentially regulated the targeting of endogenous dynamins 1 and 3 to nerve terminals, while dynamin 2 was unaffected. Specifically, when neural activity was chronically silenced for 1-2weeks by tetrodotoxin (TTX), the clustering of dynamin 1 at nerve terminals was reduced, while the clustering of dynamin 3 significantly increased. Moreover, dynamin 3 clustering was induced within hours by the sustained blockade of AMPA receptors, suggesting that AMPA receptors may function to prevent Dyn3 accumulation within nerve terminals. Clustering of dynamin 3 was induced by an antagonist of the calcium-dependent protein phosphatase calcineurin, but was not dependent upon intact actin filaments. TTX-induced clustering of Dyn3 occurred with a markedly slower time-course than the previously described clustering of synapsin 1. Potassium-induced depolarization rapidly de-clustered dynamin 3 from nerve terminals within minutes. These results, which have implications for homeostatic synapse restructuring, indicate that the three dynamins have evolved different regulatory mechanisms for trafficking to and from nerve terminals in response to changes in neural activity.