Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth.
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.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China.|Graduate School, University of Chinese Academy of Sciences, Beijing 100039, China.
Chenchang
C
Xu
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China.|Graduate School, University of Chinese Academy of Sciences, Beijing 100039, China.
Xiuping
X
Fu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China.
Shaoxia
S
Zhu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China jjliu@genetics.ac.cn.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China.
Jia-Jia
JJ
Liu
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003712:Dendrites; D004705:Endocytosis; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000378:metabolism* / Q000502:physiology*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D002966:Clathrin; C115472:Cyfip1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C504641:endophilin A1 protein, mouse; C569742:retrolinkin protein, mouse; D020813:Receptor, trkB