Rab27a and Rab27b control different steps of the exosome secretion pathway

MATIAS OSTROWSKI; NUNO B. CARMO; SOPHIE KRUMEICH; ISABELLE FANGET; GRAÇA RAPOSO; ARIEL SAVINA; CATARINA F MOITA; KRISTINE SCHAUER; ALISTAIR N. HUME; RUI P. FREITAS; BRUNO GOUD; PHILIPPE BENAROCH; NIR HACOHEN; MITSUNORI FUKUDA; CLAIRE DESNOS; MIGUEL C. SEABRA; FRANÇOIS DARCHEN; SEBASTIAN AMIGORENA; LUIS F. MOITA; CLOTILDE THERY

NATURE CELL BIOLOGY.

Año: 2009

1465-7392

<!-- /* Font Definitions */ @font-face {font-family:"Times New Roman"; panose-1:0 2 2 6 3 5 4 5 2 3; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:50331648 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman";} table.MsoNormalTable {mso-style-parent:""; font-size:10.0pt; font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 70.85pt 70.85pt 70.85pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes are secreted by several cell types and 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 a short hairpin RNA interference screen, we identified 5 small GTPases of the Rab family that promote exosome secretion in HeLa cells, including Rab27a and Rab27b. Silencing of Rab27a or Rab27b induced inhibition of MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed toward the perinuclear region upon Rab27b silencing, which reduced their density beneath the plasma membrane. Thus, the two Rab27 isoforms play different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 and Slac2b, inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. By showing that inhibition of exosome secretion is associated with alterations of MVEs, we demonstrate that exosomes mainly originate from MVEs.