RGD Reference Report - Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin. - Rat Genome Database

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

Authors: Wong, Yu-Hui  Lee, Chia-Ming  Xie, Wenjun  Cui, Bianxiao  Poo, Mu-ming 
Citation: Wong YH, etal., Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4475-84. doi: 10.1073/pnas.1511830112. Epub 2015 Jul 27.
RGD ID: 13702162
Pubmed: (View Article at PubMed) PMID:26216953
DOI: Full-text: DOI:10.1073/pnas.1511830112

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.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Syt6  (synaptotagmin 6)


Additional Information