RRC ID 72143
Author Matsui T, Sakamaki Y, Nakashima S, Fukuda M.
Title Rab39 and its effector UACA regulate basolateral exosome release from polarized epithelial cells.
Journal Cell Rep
Abstract 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.
Volume 39(9)
Pages 110875
Published 2022-5-31
DOI 10.1016/j.celrep.2022.110875
PII S2211-1247(22)00650-7
PMID 35649370
MeSH Animals Cell Membrane / metabolism Dogs Exosomes* / metabolism Madin Darby Canine Kidney Cells Multivesicular Bodies / metabolism rab GTP-Binding Proteins / metabolism
Resource
DNA material pMRX-puro-3×FLAG-UACA (RDB19594) pMRX-puro-3×FLAG-UACA-ΔANKR (RDB19595) pMRX-puro-3×FLAG-UACA-ΔCC1 (RDB19596) pMRX-puro-3×FLAG-UACA-ΔCC2 (RDB19597) pMRX-puro-3×FLAG-UACA-ΔCC3 (RDB19598) pMRX-puro-3×FLAG-UACA-ΔCC4 (RDB19599) pMRX-puro-3×Myc-Lyspersin (RDB19600)