EHD1 regulates β1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration

Citations Over TimeTop 10% of 2007 papers

Abstract

beta1 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 beta1 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 beta1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of beta1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD1-knockout mice (Ehd1(-/-) MEF) exhibited lower overall levels of beta1 integrins on the plasma membrane, but higher cell-surface-expressed activated beta1 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 beta1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.

Related Papers

• → Complementation of dominant suppression implicates CD98 in integrin activation(1997)288 cited
• → N-Glycosylation of ß4 Integrin Controls the Adhesion and Motility of Keratinocytes(2011)45 cited
• → Integrin heterodimer and receptor complexity in avian and mammalian cells.(1989)151 cited
• → The 3′UTR of the α6 integrin message regulates localization of α6β4 integrin heterodimers(2019)3 cited
• → Abstract P117: A Conserved Trans-membrane Domain Lysine in the Integrin Beta1 Subunit Regulates Renal Collecting Duct Cell Function(2016)