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Mol Biol Cell. 2016 Nov 1;27(21):3342-3356. Epub 2016 Sep 7.

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

Xu C1,2,3, Fu X2,3, Zhu S1,2, Liu JJ4,2.

Author information

1
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
2
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China.
3
Graduate School, University of Chinese Academy of Sciences, Beijing 100039, China.
4
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China jjliu@genetics.ac.cn.

Abstract

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.

PMID:
27605705
PMCID:
PMC5170866
DOI:
10.1091/mbc.E16-05-0326
[Indexed for MEDLINE]
Free PMC Article

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