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First published online 6 February 2007
doi: 10.1242/jcs.03383

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EHD1 regulates 1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration

Marko Jovi¹, Naava Naslavsky¹, Debora Rapaport², Mia Horowitz² and Steve Caplan^1,*

¹ Department of Biochemistry and Molecular Biology and Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA
² Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel

^* Author for correspondence (e-mail: scaplan{at}unmc.edu)

Accepted 27 December 2006

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 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 1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of 1 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 1 integrins on the plasma membrane, but higher cell-surface-expressed activated 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 1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.

Key words: EHD1, 1 integrin, Recycling, Focal adhesions, Motility, Cell spreading

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