RRC ID 68747
Author Kajimoto T, Okada T, Miya S, Zhang L, Nakamura S.
Title Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes.
Journal Nat Commun
Abstract During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs.
Volume 4
Pages 2712
Published 2013-1-1
DOI 10.1038/ncomms3712
PII ncomms3712
PMID 24231649
MeSH Adsorption Bacterial Proteins / metabolism Cell Membrane / metabolism Endosomes / metabolism* Exosomes / metabolism* Fluorescence Recovery After Photobleaching Fluorescence Resonance Energy Transfer Green Fluorescent Proteins / metabolism HeLa Cells Human Umbilical Vein Endothelial Cells Humans Luminescent Proteins / metabolism Lysophospholipids / metabolism Lysosomes / metabolism Protein Transport RNA, Small Interfering / metabolism Receptors, G-Protein-Coupled / metabolism Receptors, Lysosphingolipid / metabolism* Signal Transduction Sphingosine / analogs & derivatives Sphingosine / metabolism Tetraspanin 30 / metabolism
IF 12.121
Human and Animal Cells HeLa(RCB0007)