Journal
JOURNAL OF CELL SCIENCE
Volume 120, Issue 5, Pages 802-814Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.03383
Keywords
EHD1; beta 1 integrin; recycling; focal adhesions; motility; cell spreading
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Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR018759, P20RR016469] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM074876] Funding Source: NIH RePORTER
- NCRR NIH HHS [P20 RR018759, P20 RR16469] Funding Source: Medline
- NIGMS NIH HHS [1R01 GM074876-01] Funding Source: Medline
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beta 1 integrins bind to the extracellular matrix and stimulate signaling pathways leading to crucial cellular functions, including proliferation, apoptosis, cell spreading and migration. Consequently, control of beta 1 integrin function depends upon its subcellular localization, and recent studies have begun to unravel the complex regulatory mechanisms involved in integrin trafficking. We report that the C-terminal Eps15-homology (EH) domain-containing protein EHD1 plays an important role in regulating beta 1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of beta 1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD-knockout mice (Ehd1(-/-) MEF) exhibited lower overall levels of beta 1 integrins on the plasma membrane, but higher cell-surface-expressed activated beta 1 integrins, and larger, more prominent focal adhesions resulting from slower kinetics of focal adhesion disassembly. In addition, both migration and cell spreading on fibronectin were impaired in Ehd1(+/+) MEF cells, and these defects could be similarly induced by EHD1-RNAi treatment of normal Ehd1(+/+) MEF cells. They could also be rescued by transfection of wild-type EHD1 into Ehd1(-/-) MEF cells. Our data support a role for EHD1 in beta 1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.
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