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PMID: 19966785 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rab27a and Rab27b control different steps of the exosome secretion pathway.

Nature cell biology ·Vol. 12 ·No. 1 ·2010-01-00 ·Pages 19-30; sup pp 1-13

Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C

Abstract

Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.

MeSH Terms
Cell Communication Cell Membrane/metabolism Endosomes/physiology Exosomes/metabolism Flow Cytometry Fluorescent Antibody Technique Gene Silencing HeLa Cells Humans Immunoblotting RNA, Messenger/genetics,metabolism RNA, Small Interfering/pharmacology Reverse Transcriptase Polymerase Chain Reaction Subcellular Fractions Vesicular Transport Proteins/antagonists & inhibitors,genetics,metabolism rab GTP-Binding Proteins/antagonists & inhibitors,genetics,metabolism rab27 GTP-Binding Proteins
Chemicals
RNA, Messenger RNA, Small Interfering SYTL4 protein, human Vesicular Transport Proteins rab27 GTP-Binding Proteins RAB27A protein, human Rab27B protein, human rab GTP-Binding Proteins
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Ostrowski Matias
INSERM U932, 26 rue d'Ulm, 75005 Paris, France.
Carmo Nuno B
Krumeich Sophie
Fanget Isabelle
Raposo Graça
Savina Ariel
Moita Catarina F
Schauer Kristine
Hume Alistair N
Freitas Rui P
Goud Bruno
Benaroch Philippe
Hacohen Nir
Fukuda Mitsunori
Desnos Claire
Seabra Miguel C
Darchen François
Amigorena Sebastian
Moita Luis F
Thery Clotilde
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2000
Published
2010-01-00
Epub
2009-00-06
Pages
19-30; sup pp 1-13
Language
English
Region
England
NLM ID
100890575
Subset
IM
Grants
Wellcome Trust · 075498 · United Kingdom
External Links
PubMed source DOI: 10.1038/ncb2000 View journal details
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