Endocytic turnover of Rab8 controls cell polarization

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http://hdl.handle.net/10138/188608

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Vidal-Quadras , M , Holst , M R , Francis , M K , Larsson , E , Hachimi , M , Yau , W-L , Peranen , J , Martin-Belmonte , F & Lundmark , R 2017 , ' Endocytic turnover of Rab8 controls cell polarization ' , Journal of Cell Science , vol. 130 , no. 6 , pp. 1147-1157 . https://doi.org/10.1242/jcs.195420

Title: Endocytic turnover of Rab8 controls cell polarization
Author: Vidal-Quadras, Maite; Holst, Mikkel R.; Francis, Monika K.; Larsson, Elin; Hachimi, Mariam; Yau, Wai-Lok; Peranen, Johan; Martin-Belmonte, Fernando; Lundmark, Richard
Contributor organization: Medicum
University of Helsinki
Department of Anatomy
Date: 2017-03-15
Language: eng
Number of pages: 11
Belongs to series: Journal of Cell Science
ISSN: 0021-9533
DOI: https://doi.org/10.1242/jcs.195420
URI: http://hdl.handle.net/10138/188608
Abstract: Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis.
Subject: Rab8
GRAF1
Cell polarization
Endocytosis
GTPASE-ACTIVATING PROTEIN
MEMBRANE TENSION
LEADING-EDGE
EPITHELIAL MORPHOGENESIS
RECYCLING ENDOSOMES
SPINDLE ORIENTATION
POLARITY PROTEIN
APICAL SURFACE
CDC42 CONTROLS
PATHWAY
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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