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

Journal of Cell Science 120, 802-814 (2007)
Published by The Company of Biologists 2007
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Research Article

EHD1 regulates beta1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration

Marko Jovic1, Naava Naslavsky1, Debora Rapaport2, Mia Horowitz2 and Steve Caplan1,*

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

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.

Key words: EHD1, beta1 integrin, Recycling, Focal adhesions, Motility, Cell spreading




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