Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells
Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells
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DOI：
10.1016/j.celrep.2022.110875
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发表时间：
2022-05-31
期刊：
影响因子：
8.8
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Matsui, Takahide;Sakamaki, Yuriko;Fukuda, Mitsunori
外来体是源自多泡体（MVB）的管腔内囊泡的小的细胞外囊泡。我们以前报道过极化的Madin-Darby犬肾（MDCK）上皮细胞分泌两种类型的外泌体，顶端和基底外侧外泌体，从不同的MVB。然而，这些MVB如何选择性地靶向顶膜或基底膜仍然未知。在这里，我们分析了Rab家族小GTP酶的成员，并表明不同的Rab组介导不对称的外泌体释放。Rab 27是MVB转运外泌体释放的最知名调节剂，其特异性但部分参与顶端外泌体释放，Rab 37是Rab 27的密切同源物，是另外的顶端外泌体调节剂。相比之下，Rab 39作为基底外侧外泌体释放的特异性调节剂发挥作用。在机制上，Rab 39与其效应子UACA相互作用，然后UACA招募Lysperin，BLOC-1相关复合物（BORC）的一种组分。我们的研究结果表明Rab 39-UACA-BORC复合物特异性介导基底外侧外泌体释放。
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.