期刊
MOLECULAR BIOLOGY OF THE CELL
卷 22, 期 22, 页码 4380-4389出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E10-12-0936
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资金
- Swedish Cancer Society
- Swedish Medical Research Council
- Swedish foundation for strategic research
- Medical Faculty, Umea University
- Royal Swedish Academy of Sciences
- Magn Bergvall Foundation
- Harald Jeanssons Foundation
- Ake Wibergs Foundation
- National Health and Medical Research Council of Australia
- Trinity College, Cambridge
- MRC
- F
- Medical Research Council [MC_U105178795] Funding Source: researchfish
- MRC [MC_U105178795] Funding Source: UKRI
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.
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