Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions.

Nature Communications
Caspar T H JonkerJudith Klumperman

Abstract

Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.

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Citations

May 12, 2019·Journal of Cell Science·Pranshu SahgalJohanna Ivaska
Jan 23, 2020·Journal of Cell Science·Daniela SparvoliAaron P Turkewitz
Sep 20, 2020·Wiley Interdisciplinary Reviews. Cognitive Science·Peter Langland-Hassan
Apr 15, 2020·European Journal of Clinical Investigation·Sergi Masgrau-AlsinaIna Rohwedder
May 17, 2019·Journal of Cell Science·Jan van der BeekJudith Klumperman
Jan 16, 2020·International Journal of Molecular Sciences·Filipp VasilevTakanobu Otomo
Feb 1, 2019·Communications Biology·Saori NoguchiShigeomi Shimizu
Dec 15, 2020·American Journal of Human Genetics·Lourdes Ortiz-FernándezAmr H Sawalha
Oct 7, 2020·Trends in Biochemical Sciences·Martijn A NolteCoert Margadant
Jan 12, 2020·Communications Biology·Saori NoguchiShigeomi Shimizu
Mar 31, 2021·Journal of Molecular Biology·Zsófia Simon-VecseiGábor Juhász
May 4, 2021·EMBO Molecular Medicine·Kalliopi SofouFredrik H Sterky

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Methods Mentioned

BETA
GTPases
co-immunoprecipitation
co-IP
proximity ligation assay
fluorescence microscopy
ELISA
confocal microscopy
transfection
immunoprecipitation
electrophoresis

Software Mentioned

ImageJ
Fiji ImageJ
CORVET
Softworx

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