Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin.

Yu-Hui Wong, Chia-Ming Lee, Wenjun Xie, Bianxiao Cui, Mu-ming Poo

Proceedings of the National Academy of Sciences of the United States of America 2015 Aug 11

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Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation.

Citation

Yu-Hui Wong, Chia-Ming Lee, Wenjun Xie, Bianxiao Cui, Mu-ming Poo. Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin. Proceedings of the National Academy of Sciences of the United States of America. 2015 Aug 11;112(32):E4475-84