Open AccessRabgap1 promotes recycling of active β1 integrins to support effective cell migration
Author(s) -
Anna Valeria Samarelli,
Tilman Ziegler,
Alexander Meves,
Reinhard Fässler,
Ralph T. Böttcher
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.243683
Subject(s) - endosome , integrin , microbiology and biotechnology , biology , cell adhesion , focal adhesion , cell migration , internalization , cell membrane , cd49c , integrin, beta 6 , cell , collagen receptor , intracellular , signal transduction , biochemistry
Integrin function depends on the continuous internalization of integrins and their subsequent endosomal recycling to the plasma membrane to drive adhesion dynamics, cell migration and invasion. Here we assign a pivotal role of Rabgap1 (GapCenA) for the recycling of endocytosed active β1 integrins to the plasma membrane. Rabgap1 binds with its PTB domain to the membrane-proximal NPxY motif in the cytoplasmic domain of β1 integrin subunit on endosomes. Silencing Rabgap1 in mouse fibroblasts leads to the intracellular accumulation of active β1 integrins, alters focal adhesions formation and decreases cell migration and cancer cell invasion. Functionally, Rabgap1 facilitates active β1 integrin recycling to the plasma membrane through attenuation of Rab11 activity. Together our results identify Rabgap1 as important factor for conformation-specific integrin trafficking and define its role for β1 integrin-mediated cell migration in mouse fibroblast and in breast cancer cells.