肌球蛋白-5b 的调节作用由 Rab11a 和 Rab11 家族相互作用蛋白 2 介导。
Regulation of Myosin-5b by Rab11a and the Rab11 family interacting protein 2.
机构信息
Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
出版信息
Biosci Rep. 2019 Jan 8;39(1). doi: 10.1042/BSR20181252. Print 2019 Jan 31.
Mammalian myosin-5b (Myo5b) plays a critical role in the recycling of endosomes to the plasma membrane via the interactions with Rab11a and the Rab11 family interacting protein 2 (FIP2). However, it remains unclear on how Rab11a and FIP2 are coordinated in tethering Myo5b with the vesicles and activating the motor function of Myo5b. In the present study, we show that Rab11a binds to the globular tail domain (GTD) of Myo5b and this binding abolishes the head-GTD interaction of Myo5b, thus activating the motor function of Myo5b. On the other hand, FIP2 directly interacts with both Rab11a and the tail of Myo5b, and the binding of FIP2 to Myo5b does not affect Myo5b motor function. Moreover, Rab11a displays higher affinity to FIP2 than to Myo5b, suggesting that Rab11a binds preferentially to FIP2 than to Myo5b. Based on the current findings, we propose that the association of Myo5b with vesicles is mediated by FIP2, which bridges Myo5b and the membrane-bound Rab11a, whereas the motor function of Myo5b is regulated by Rab11a.
哺乳动物肌球蛋白-5b（Myo5b）在通过与 Rab11a 和 Rab11 家族相互作用蛋白 2（FIP2）的相互作用将内体再循环到质膜中起着关键作用。然而，Rab11a 和 FIP2 如何协调将 Myo5b 与囊泡连接并激活 Myo5b 的运动功能仍不清楚。在本研究中，我们表明 Rab11a 与 Myo5b 的球状尾部结构域（GTD）结合，该结合破坏了 Myo5b 的头部-GTD 相互作用，从而激活了 Myo5b 的运动功能。另一方面，FIP2 直接与 Rab11a 和 Myo5b 的尾部相互作用，并且 FIP2 与 Myo5b 的结合不影响 Myo5b 的运动功能。此外，Rab11a 与 FIP2 的亲和力高于与 Myo5b 的亲和力，表明 Rab11a 优先与 FIP2 而不是与 Myo5b 结合。基于目前的发现，我们提出 Myo5b 与囊泡的结合是由 FIP2 介导的，FIP2 桥接 Myo5b 和膜结合的 Rab11a，而 Myo5b 的运动功能由 Rab11a 调节。
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