Rab27a and Rab27b control different steps of the exosome secretion pathway

被引：2047

作者：

Ostrowski, Matias ^{[2
,3
]}

Carmo, Nuno B. ^{[1
]}

Krumeich, Sophie ^{[2
,3
]}

Fanget, Isabelle ^{[10
]}

Raposo, Graca ^{[3
,4
]}

Savina, Ariel ^{[2
,3
]}

Moita, Catarina F. ^{[1
]}

Schauer, Kristine ^{[3
,4
]}

Hume, Alistair N. ^{[5
]}

Freitas, Rui P. ^{[1
]}

Goud, Bruno ^{[3
,4
]}

Benaroch, Philippe ^{[2
,3
]}

Hacohen, Nir ^{[8
,9
]}

Fukuda, Mitsunori ^{[11
]}

Desnos, Claire ^{[10
]}

Seabra, Miguel C. ^{[5
,6
,7
]}

Darchen, Francois ^{[10
]}

Amigorena, Sebastian ^{[2
,3
]}

Moita, Luis F. ^{[1
]}

Thery, Clotilde ^{[2
,3
]}

机构：

[1] Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal

[2] INSERM, U932, F-75005 Paris, France

[3] Inst Curie, F-75005 Paris, France

[4] CNRS, UMR144, F-75005 Paris, France

[5] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England

[6] Univ Nova Lisboa, Fac Ciencias Med, CEDOC, P-1169056 Lisbon, Portugal

[7] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal

[8] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02142 USA

[9] Harvard & MIT, Broad Inst, Cambridge, MA USA

[10] CNRS, Inst Biol Physicochim, FRE 3146, F-75005 Paris, France

[11] Tohoku Univ, Dept Dev Biol & Neurosci, Lab Membrane Trafficking Mech, Sendai, Miyagi 9809578, Japan

来源：

NATURE CELL BIOLOGY | 2010年 / 12卷 / 01期

关键词：

CELL-DERIVED EXOSOMES; MULTIVESICULAR ENDOSOMES; PLASMA-MEMBRANE; B-LYMPHOCYTES; VESICLES; PROTEINS; GRANULES; RELEASE; GTPASES; ASSOCIATION;

D O I：

10.1038/ncb2000

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：19 / U61

页数：25

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