Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells.

Takahide Matsui, Yuriko Sakamaki, Shumpei Nakashima, Mitsunori Fukuda

Cell reports 2022 May 31

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Takahide Matsui, Yuriko Sakamaki, Shumpei Nakashima, Mitsunori Fukuda. Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells. Cell reports. 2022 May 31;39(9):110875