Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth.
Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth.
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Retrolinkin 招募 WAVE1 蛋白复合物以促进 BDNF 诱导的 TrkB 内吞作用和树突生长
DOI：
10.1091/mbc.e16-05-0326
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发表时间：
2016-11-01
影响因子：
3.3
通讯作者：
Liu JJ
中科院分区：
文献类型：
--
作者：
Xu C;Fu X;Zhu S;Liu JJ
Retrolinkin是一种神经元膜蛋白，与肌动蛋白成核促进因子的WAVE 1复合物相互作用。Retrolinkin将WAVE 1募集到质膜以激活Arp 2/3依赖性肌动蛋白聚合，这是树突发育期间BDNF诱导的TrkB内吞和信号传导所需的。Retrolinkin是一种神经元膜蛋白，与内啡肽A1协同作用，介导CNS神经元树突中脑源性神经营养因子（BDNF）及其受体原肌球蛋白相关激酶B（Trk B）之间形成的配体-受体复合物的早期内吞运输和信号转导。在这里，我们报告了逆转录蛋白与WAVE 1复合物的CYFIP 1/2亚基相互作用，WAVE 1复合物是WASP/WAVE成核促进因子家族的成员，它结合并激活Arp 2/3复合物以促进分支肌动蛋白聚合。WAVE 1，而不是N-WASP，是BDNF诱导的TrkB内吞和树突生长所必需的。逆转录蛋白和CYFIP 1/2之间的相互作用的破坏损害招募WAVE 1的神经元质膜BDNF添加后，阻断激活的TrkB的内化。我们还表明，WAVE 1介导的BDNF激活的TrkB的内吞作用是肌动蛋白依赖和网格蛋白独立。这些结果不仅揭示了retrolinkin在BDNF-TrkB内吞作用中的机制作用，而且还表明内吞作用期间WASP/WAVE依赖性肌动蛋白聚合受到细胞类型特异性和货物特异性调节剂的调节。
Retrolinkin, a neuronal membrane protein, interacts with the WAVE1 complex of actin nucleation–promoting factors. Retrolinkin recruits WAVE1 to the plasma membrane to activate Arp2/3-dependent actin polymerization, which is required for BDNF-induced TrkB endocytosis and signaling during dendrite development. 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.