QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 8, 3589-3598, August 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E08-01-0085v1 19/8/3589    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Helsten, T. L. Articles by Shattil, S. J. Search for Related Content PubMed PubMed Citation Articles by Helsten, T. L. Articles by Shattil, S. J.

Differences in Regulation of Drosophila and Vertebrate Integrin Affinity by Talin

Teresa L. Helsten^*, Thomas A. Bunch, Hisashi Kato^*, Jun Yamanouchi^*, Sharon H. Choi^*, Alison L. Jannuzi, Chloe C. Féral^*, Mark H. Ginsberg^*, Danny L. Brower^,,, and Sanford J. Shattil^*

*Department of Medicine, University of California, San Diego, La Jolla, CA 92093; and Departments of Molecular and Cellular Biology and Biochemistry, Arizona Cancer Center, Tucson, AZ 85724

Submitted January 28, 2008; Revised April 23, 2008; Accepted May 15, 2008
Monitoring Editor: Jean E. Schwarzbauer

Integrin-mediated cell adhesion is essential for development of multicellular organisms. In worms, flies, and vertebrates, talin forms a physical link between integrin cytoplasmic domains and the actin cytoskeleton. Loss of either integrins or talin leads to similar phenotypes. In vertebrates, talin is also a key regulator of integrin affinity. We used a ligand-mimetic Fab fragment, TWOW-1, to assess talin's role in regulating Drosophila PS2βPS affinity. Depletion of cellular metabolic energy reduced TWOW-1 binding, suggesting PS2βPS affinity is an active process as it is for vertebrate integrins. In contrast to vertebrate integrins, neither talin knockdown by RNA interference nor talin head overexpression had a significant effect on TWOW-1 binding. Furthermore, replacement of the transmembrane or talin-binding cytoplasmic domains of PS2βPS with those of human IIbβ3 failed to enable talin regulation of TWOW-1 binding. However, substitution of the extracellular and transmembrane domains of PS2βPS with those of IIbβ3 resulted in a constitutively active integrin whose affinity was reduced by talin knockdown. Furthermore, wild-type IIbβ3 was activated by overexpression of Drosophila talin head domain. Thus, despite evolutionary conservation of talin's integrin/cytoskeleton linkage function, talin is not sufficient to regulate Drosophila PS2βPS affinity because of structural features inherent in the PS2βPS extracellular and/or transmembrane domains.

Deceased.

Address correspondence to: Teresa L. Helsten (thelsten{at}ucsd.edu)

Abbreviations used: CHO, Chinese hamster ovary; GFP, green fluorescence protein; shRNA, short hairpin RNA; BSA, bovine serum albumin; PBS, phosphate-buffered saline; RNAi, RNA interference.

This article has been cited by other articles:

				D. S. Harburger and D. A. Calderwood Integrin signalling at a glance J. Cell Sci., January 15, 2009; 122(2): 159 - 163. [Full Text] [PDF]

				E. Puklin-Faucher and M. P. Sheetz The mechanical integrin cycle J. Cell Sci., January 15, 2009; 122(2): 179 - 186. [Abstract] [Full Text] [PDF]