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First published online 25 May 2004
doi: 10.1242/jcs.01156

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A NHERF binding site links the ßPDGFR to the cytoskeleton and regulates cell spreading and migration

¹ Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
² Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA

^* Author for correspondence (e-mail: ramesh{at}helix.mgh.harvard.edu)

Accepted 12 February 2004

The Na⁺/H⁺ exchanger regulatory factor, NHERF, is a multifunctional adapter protein involved in a wide range of physiological activities. NHERF associates with merlin and the ezrin/radixin/moesin (MERM) family of membrane-actin cytoskeletal linker proteins through its C-terminus and is capable of interacting via its PDZ1 domain to the ßPDGF receptor (ßPDGFR). Thus, NHERF, potentially links the ßPDGFR to the actin cytoskeleton through its interaction with MERM proteins. In the present study, we have examined whether abolishing the interaction of ßPDGFR with NHERF results in actin cytoskeletal rearrangements. We have stably expressed a wild-type ßPDGFR, a mutant ßPDGFR (L1106A) that is incapable of interacting with NHERF, as well as a kinase defective mutant receptor (K634R), in PDGFR-deficient mouse embryonic fibroblasts. Our observations indicate that cells expressing ßPDGFR (L1106A) were impaired in their ability to spread and migrate on fibronectin compared with wild-type and K634R cells. L1106A mutant cells also revealed an increased number of focal adhesions, a condensed F-actin ring at the cell periphery and a decrease in total focal adhesion kinase (FAK) tyrosine phosphorylation. Further, we show that NHERF and MERM proteins could act as intermediary bridging proteins between ßPDGFR and FAK. Thus, the interaction of ßPDGFR with NHERF may provide an essential link between the cell membrane and the cortical actin cytoskeleton independent of receptor activity.

Key words: ßPDGFR, NHERF, Cell spreading, Migration, Merlin, ERM

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