The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading

Doherty, Gary J., Ahlund, Monika K., Howes, Mark T., Moren, Bjorn, Parton, Robert G., McMahon, Harvey T. and Lundmark, Richard (2011) The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading. Molecular Biology of the Cell, 22 22: 4380-4389. doi:10.1091/mbc.E10-12-0936

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Author Doherty, Gary J.
Ahlund, Monika K.
Howes, Mark T.
Moren, Bjorn
Parton, Robert G.
McMahon, Harvey T.
Lundmark, Richard
Title The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1059-1524
Publication date 2011-11-15
Sub-type Article (original research)
DOI 10.1091/mbc.E10-12-0936
Open Access Status File (Publisher version)
Volume 22
Issue 22
Start page 4380
End page 4389
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Collection year 2012
Language eng
Abstract The rho GTPase-activating protein GTPase regulator associated with focal adhesion kinase-1 (GRAF1) remodels membranes into tubulovesicular clathrin-independent carriers (CLICs) mediating lipid-anchored receptor endocytosis. However, the cell biological functions of this highly prevalent endocytic pathway are unclear. In this article, we present biochemical and cell biological evidence that GRAF1 interacted with a network of endocytic and adhesion proteins and was found enriched at podosome-like adhesions and src-induced podosomes. We further demonstrate that these sites comprise microdomains of highly ordered lipid enriched in GRAF1 endocytic cargo. GRAF1 activity was upregulated in spreading cells and uptake via CLICs was concentrated at the leading edge of migrating cells. Depletion of GRAF1, which inhibits CLIC generation, resulted in profound defects in cell spreading and migration. We propose that GRAF1 remodels membrane microdomains at adhesion sites into endocytic carriers, facilitating membrane turnover during cell morphological changes.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 22 times in Scopus Article | Citations
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