BDNF Regulates Rab11-Mediated Recycling Endosome Dynamics to Induce Dendritic Branching

Dendritic arborization of neurons is regulated by brain-derived neurotrophic factor (BDNF) together with its receptor, TrkB. Endocytosis is required for dendritic branching and regulates TrkB signaling, but how postendocytic trafficking determines the neuronal response to BDNF is not well understood. The monomeric GTPase Rab11 regulates the dynamics of recycling endosomes and local delivery of receptors to specific dendritic compartments. We investigated whether Rab11-dependent trafficking of TrkB in dendrites regulates BDNF-induced dendritic branching in rat hippocampal neurons. We report that TrkB in dendrites is a cargo for Rab11 endosomes and that both Rab11 and its effector, MyoVb, are required for BDNF/TrkB-induced dendritic branching. In addition, BDNF induces the accumulation of Rab11-positive endosomes and GTP-bound Rab11 in dendrites and the expression of a constitutively active mutant of Rab11 is sufficient to increase dendritic branching by increasing TrkB localization in dendrites and enhancing sensitization to endogenous BDNF. We propose that Rab11-dependent dendritic recycling provides a mechanism to retain TrkB in dendrites and to increase local signaling to regulate arborization.Published in The Journal of Neuroscience: http://www.jneurosci.org/content/33/14/6112. Grants: This work was supported by FONDECYT (Grants 1085273 and 1120146 to F.C.B.), Millennium Science Initiative (MINREB P07/011-F and CARE-PFB-12/2007 to F.C.B.; P09-015-F to A.C.), the National Institutes of Health (Grant NIH R01 MH080738 and a Whitehall Foundation award to R.K.)