Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles.
By transporting regulatory RNAs like microRNAs, extracellular vesicles provide a novel layer of intercellular gene regulation. However, the underlying secretory pathways and the mechanisms of cargo selection are poorly understood. Rab GTPases are central coordinators of membrane trafficking with distinct members of this family being responsible for specific transport pathways. Here we identified a vesicular export mechanism for miR-143, induced by the shear stress responsive transcription factor KLF2, and demonstrate its dependency on Rab7a/Rab27b in endothelial cells.
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
Nicolas
N
Jaé
Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany.
David G
DG
McEwan
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
Yosif
Y
Manavski
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
Reinier A
RA
Boon
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt am Main, Germany. Electronic address: dimmeler@em.uni-frankfurt.de.
Stefanie
S
Dimmeler
D015153:Blotting, Western; D002478:Cells, Cultured; D000067128:Extracellular Vesicles / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D000090802:rab7 GTP-Binding Proteins; C512960:Rab27B protein, human; D020691:rab GTP-Binding Proteins
Endothelial cell; Exosome; Microvesicle; Rab protein; microRNA