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Published online 11 December 2000. doi:10.1083/jcb.151.6.1141
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© The Rockefeller University Press, 0021-9525/2000//1141 $5.00
The Journal of Cell Biology, Volume 151, Number 6, , 2000 1141-1154

Original Article

Nischarin, a Novel Protein That Interacts with the Integrin {alpha}5 Subunit and Inhibits Cell Migration



Suresh K. Alaharia, Jung Weon Leea, and Rudy L. Julianoa

a Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599
CB# 7365, ME Jones Bldg., Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599.(919) 966-5640(919) 966-4343

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 {alpha} and β 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 {alpha}5 subunit, inhibits cell motility, and alters actin filament organization. Nischarin is primarily a cytosolic protein, but clearly associates with {alpha}5β1, as demonstrated by coimmunoprecipitation. Overexpression of Nischarin markedly reduces {alpha}5β1-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

© 2000 The Rockefeller University Press

Abbreviations used in this paper: FAK, focal adhesion kinase; GFP, green fluorescent protein; ORF, open reading frame; REF, rat embryonic fibroblast; RIE, rat intestinal epithelial.


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