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

Chenchang Xu, Xiuping Fu, Shaoxia Zhu, Jia Jia Liu

Research output: Contribution to journalArticle

Abstract

Retrolinkin, a neuronal membrane protein, coordinates with endophilin A1 and mediates early endocytic traffcking and signal transduction of the ligand-receptor complex formed between brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosinrelated 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-specifc and cargo-specifc modulators.

Original languageEnglish (US)
Pages (from-to)3342-3356
Number of pages15
JournalMolecular Biology of the Cell
Volume27
Issue number21
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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