JCB logo
IN Cell Analyzer 2000
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 11 December 2000. doi:10.1083/jcb.151.6.1141
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 557K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alahari, S. K.
Right arrow Articles by Juliano, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alahari, S. K.
Right arrow Articles by Juliano, R. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© 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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents