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Publication : Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth.

First Author  Xu C Year  2016
Journal  Mol Biol Cell Volume  27
Issue  21 Pages  3342-3356
PubMed ID  27605705 Mgi Jnum  J:239183
Mgi Id  MGI:5825407 Doi  10.1091/mbc.E16-05-0326
Citation  Xu C, et al. (2016) Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth. Mol Biol Cell 27(21):3342-3356
abstractText  Retrolinkin, a neuronal membrane protein, coordinates with endophilin A1 and mediates early endocytic trafficking and signal transduction of the ligand-receptor complex formed between brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), in dendrites of CNS neurons. Here we report that retrolinkin interacts with the CYFIP1/2 subunit of the WAVE1 complex, a member of the WASP/WAVE family of nucleation-promoting factors that binds and activates the Arp2/3 complex to promote branched actin polymerization. WAVE1, not N-WASP, is required for BDNF-induced TrkB endocytosis and dendrite outgrowth. Disruption of the interaction between retrolinkin and CYFIP1/2 impairs recruitment of WAVE1 to neuronal plasma membrane upon BDNF addition and blocks internalization of activated TrkB. We also show that WAVE1-mediated endocytosis of BDNF-activated TrkB is actin dependent and clathrin independent. These results not only reveal the mechanistic role of retrolinkin in BDNF-TrkB endocytosis, but also indicate that WASP/WAVE-dependent actin polymerization during endocytosis is regulated by cell type-specific and cargo-specific modulators.
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