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Original Article |
5 Subunit and Inhibits Cell Migration
Correspondence to: Suresh K. Alahari, CB# 7365, ME Jones Bldg., Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599. Tel:(919) 966-4343 Fax:(919) 966-5640 E-mail:alahari{at}med.unc.edu.
Integrins have been implicated in key cellular functions, including cytoskeletal organization, motility, growth, survival, and control of gene expression. The plethora of integrin and ß subunits suggests that individual integrins have unique biological roles, implying specific molecular connections between integrins and intracellular signaling or regulatory pathways. Here, we have used a yeast two-hybrid screen to identify a novel protein, termed Nischarin, that binds preferentially to the cytoplasmic domain of the integrin 5 subunit, inhibits cell motility, and alters actin filament organization. Nischarin is primarily a cytosolic protein, but clearly associates with 5ß1, as demonstrated by coimmunoprecipitation. Overexpression of Nischarin markedly reduces 5ß1-dependent cell migration in several cell types. Rat embryo fibroblasts transfected with Nischarin constructs have "basket-like" networks of peripheral actin filaments, rather than typical stress fibers. These observations suggest that Nischarin might affect signaling to the cytoskeleton regulated by Rho-family GTPases. In support of this, Nischarin expression reverses the effect of Rac on lamellipodia formation and selectively inhibits Rac-mediated activation of the c-fos promoter. Thus, Nischarin may play a negative role in cell migration by antagonizing the actions of Rac on cytoskeletal organization and cell movement.
Key Words: integrin, Rac, cell migration, cytoskeleton, two hybrid
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