title: Rab27a and Rab27b control different steps of the exosome secretion pathway.
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.
authors: INSERM U932, 26 rue d'Ulm, 75005 Paris, France.
authors: Matias
authors: M
authors: Ostrowski
authors: Nuno B
authors: NB
authors: Carmo
authors: Sophie
authors: S
authors: Krumeich
authors: Isabelle
authors: I
authors: Fanget
authors: Graça
authors: G
authors: Raposo
authors: Ariel
authors: A
authors: Savina
authors: Catarina F
authors: CF
authors: Moita
authors: Kristine
authors: K
authors: Schauer
authors: Alistair N
authors: AN
authors: Hume
authors: Rui P
authors: RP
authors: Freitas
authors: Bruno
authors: B
authors: Goud
authors: Philippe
authors: P
authors: Benaroch
authors: Nir
authors: N
authors: Hacohen
authors: Mitsunori
authors: M
authors: Fukuda
authors: Claire
authors: C
authors: Desnos
authors: Miguel C
authors: MC
authors: Seabra
authors: François
authors: F
authors: Darchen
authors: Sebastian
authors: S
authors: Amigorena
authors: Luis F
authors: LF
authors: Moita
authors: Clotilde
authors: C
authors: Thery
mesh_terms: D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000502:physiology*; D055354:Exosomes / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C512779:SYTL4 protein, human; D033921:Vesicular Transport Proteins; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; C512960:Rab27B protein, human; D020691:rab GTP-Binding Proteins