Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Microscopy Research Support Unit Research Core, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Cell Rep. 2022 May 31;39(9):110875. doi: 10.1016/j.celrep.2022.110875.
Exosomes are small extracellular vesicles that originate from the intraluminal vesicles of multivesicular bodies (MVBs). We previously reported that polarized Madin-Darby canine kidney (MDCK) epithelial cells secrete two types of exosomes, apical and basolateral exosomes, from different MVBs. However, how these MVBs are selectively targeted to the apical or basolateral membrane remained unknown. Here, we analyze members of the Rab family small GTPases and show that different sets of Rabs mediate asymmetrical exosome release. Rab27, the best-known regulator of MVB transport for exosome release, is specifically but partially involved in apical exosome release, and Rab37, a close homolog of Rab27, is an additional apical exosome regulator. By contrast, Rab39 functions as a specific regulator of basolateral exosome release. Mechanistically, Rab39 interacts with its effector UACA, and UACA then recruits Lyspersin, a component of BLOC-1-related complex (BORC). Our findings suggest that the Rab39-UACA-BORC complex specifically mediates basolateral exosome release.
外泌体是源自多泡体（MVB）腔内囊泡的小型细胞外囊泡。我们之前报道过极化的犬肾细胞（MDCK）上皮细胞从不同的 MVB 分泌两种类型的外泌体，即顶端和基底外侧外泌体。然而，这些 MVB 如何被选择性地靶向到顶端或基底外侧膜仍然未知。在这里，我们分析了 Rab 家族小 GTPase 的成员，并表明不同的 Rab 家族小 GTPase 介导不对称的外泌体释放。Rab27 是已知的 MVB 运输调节因子，对 exosome 释放具有特异性，但部分参与顶端外泌体释放，Rab37 是 Rab27 的密切同源物，是另一个顶端外泌体调节因子。相比之下，Rab39 作为基底外侧外泌体释放的特异性调节因子发挥作用。从机制上讲，Rab39 与它的效应物 UACA 相互作用，然后 UACA 招募 Lyspersin，这是 BLOC-1 相关复合物（BORC）的一个组成部分。我们的发现表明，Rab39-UACA-BORC 复合物特异性地介导基底外侧外泌体释放。
