EHD1 regulates β1 integrin endosomal transport

Effects on focal adhesion, cell spreading and migration

Marko Jović, Naava Naslavsky, Debora Rapaport, Mia Horowitz, Steven H Caplan

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

β1 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 β1 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 β1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of β1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD1-knockout mice (Ehdi-/- MEF) exhibited lower overall levels of β1 integrins on the plasma membrane, but higher cell-surface-expressed activated β1 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 β1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.

Original languageEnglish (US)
Pages (from-to)802-814
Number of pages13
JournalJournal of Cell Science
Volume120
Issue number5
DOIs
StatePublished - Mar 1 2007

Fingerprint

Focal Adhesions
Integrins
Cell Movement
Fibroblasts
Recycling
RNA Interference
Transferrin
Fibronectins
Knockout Mice
Extracellular Matrix
Transfection
Cell Membrane
Apoptosis

Keywords

  • Cell spreading
  • EHD1
  • Focal adhesion
  • Motility
  • Recycling
  • β1 integrin

ASJC Scopus subject areas

  • Cell Biology

Cite this

EHD1 regulates β1 integrin endosomal transport : Effects on focal adhesion, cell spreading and migration. / Jović, Marko; Naslavsky, Naava; Rapaport, Debora; Horowitz, Mia; Caplan, Steven H.

In: Journal of Cell Science, Vol. 120, No. 5, 01.03.2007, p. 802-814.

Research output: Contribution to journalArticle

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