Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Traffic. 2013 Sep;14(9):949-63. doi: 10.1111/tra.12083. Epub 2013 Jun 10.
Rab27, a member of the small GTPase Rab family, is widely conserved in metazoan, and two Rab27 isoforms, Rab27A and Rab27B, are present in vertebrates. Rab27A was the first Rab protein whose dysfunction was found to cause a human hereditary disease, type 2 Griscelli syndrome, which is characterized by silvery hair and immunodeficiency. The discovery in the 21st century of three distinct types of mammalian Rab27A effectors [synaptotagmin-like protein (Slp), Slp homologue lacking C2 domains (Slac2), and Munc13-4] that specifically bind active Rab27A has greatly accelerated our understanding not only of the molecular mechanisms of Rab27A-mediated membrane traffic (e.g. melanosome transport and regulated secretion) but of the symptoms of Griscelli syndrome patients at the molecular level. Because Rab27B is widely expressed in various tissues together with Rab27A and has been found to have the ability to bind all of the Rab27A effectors that have been tested, Rab27A and Rab27B were initially thought to function redundantly by sharing common Rab27 effectors. However, recent evidence has indicated that by interacting with different Rab27 effectors Rab27A and Rab27B play different roles in special types of secretion (e.g. exosome secretion and mast cell secretion) even within the same cell type. In this review article, I describe the current state of our understanding of the functions of Rab27 effectors in secretory pathways.
Rab27，小 GTPase Rab 家族的一员，在后生动物中广泛保守，两种 Rab27 同工型，Rab27A 和 Rab27B，存在于脊椎动物中。Rab27A 是第一个被发现功能障碍导致人类遗传性疾病 2 型 Griscelli 综合征的 Rab 蛋白，其特征是银白色的头发和免疫缺陷。在 21 世纪，发现了三种不同类型的哺乳动物 Rab27A 效应物 [突触结合蛋白样蛋白 (Slp)、缺乏 C2 结构域的 Slp 同源物 (Slac2) 和 Munc13-4]，它们特异性结合活性 Rab27A，这极大地加速了我们对 Rab27A 介导的膜运输（例如黑素体运输和调节分泌）分子机制的理解，也加速了对 Griscelli 综合征患者分子水平症状的理解。因为 Rab27B 与 Rab27A 一起在各种组织中广泛表达，并已被发现具有结合所有已测试的 Rab27A 效应物的能力，所以 Rab27A 和 Rab27B 最初被认为通过共享共同的 Rab27 效应物而具有冗余功能。然而，最近的证据表明，Rab27A 和 Rab27B 通过与不同的 Rab27 效应物相互作用，即使在同一细胞类型中，也在特殊类型的分泌（例如外泌体分泌和肥大细胞分泌）中发挥不同的作用。在这篇综述文章中，我描述了我们对 Rab27 效应物在分泌途径中的功能的理解现状。
