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作 者:Tianlun Ding Jinyao Ji Weiying Zhang Yuheng Liu Boqi Liu Yiyang Han Chunlai Chen Li Yu
机构地区:[1]State Key Laboratory of Membrane Biology,Tsinghua University-Peking University Joint Center for Life Sciences,Beijing Frontier Research Center for Biological Structure,School of Life Sciences,Tsinghua University,Beijing,China [2]School of Life Sciences,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center of Biological Structure,Tsinghua University,Beijing,China [3]State Key Laboratory of Membrane Biology,Tsinghua University-Peking University Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China
出 处:《Cell Research》2023年第8期617-627,共11页细胞研究(英文版)
基 金:the National Natural Science Foundation of China(32030023 and 92054301);Beijing Municipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Z221100003422012);Tsinghua University Initiative Scientific Research Program(20221080007)。
摘 要:Migrasomes are recently discovered organelles,which are formed on the ends or branch points of retraction fibers at the trailing edge of migrating cells.Previously,we showed that recruitment of integrins to the site of migrasome formation is essential for migrasome biogenesis.In this study,we found that prior to migrasome formation,PIP5K1A,a PI4P kinase which converts PI4P into PI(4,5)P_(2),is recruited to migrasome formation sites.The recruitment of PIP5K1A results in generation of PI(4,5)P_(2) at the migrasome formation site.Once accumulated,PI(4,5)P_(2) recruits Rab35 to the migrasome formation site by interacting with the C-terminal polybasic cluster of Rab35.We further demonstrated that active Rab35 promotes migrasome formation by recruiting and concentrating integrinα5 at migrasome formation sites,which is likely mediated by the interaction between integrinα5 and Rab35.Our study identifies the upstream signaling events orchestrating migrasome biogenesis.
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