Repository logo
 

Alternative mechanisms for talin to mediate integrin function.


Change log

Authors

Herbert, Samantha L 
Wellmann, Jutta 
Johnson, Robert 
Parsons, Maddy 

Abstract

Cell-matrix adhesion is essential for building animals, promoting tissue cohesion, and enabling cells to migrate and resist mechanical force. Talin is an intracellular protein that is critical for linking integrin extracellular-matrix receptors to the actin cytoskeleton. A key question raised by structure-function studies is whether talin, which is critical for all integrin-mediated adhesion, acts in the same way in every context. We show that distinct combinations of talin domains are required for each of three different integrin functions during Drosophila development. The partial function of some mutant talins requires vinculin, indicating that recruitment of vinculin allows talin to duplicate its own activities. The different requirements are best explained by alternative mechanisms of talin function, with talin using one or both of its integrin-binding sites. We confirmed these alternatives by showing that the proximity between the second integrin-binding site and integrins differs, suggesting that talin adopts different orientations relative to integrins. Finally, we show that vinculin and actomyosin activity help change talin's orientation. These findings demonstrate that the mechanism of talin function differs in each developmental context examined. The different arrangements of the talin molecule relative to integrins suggest that talin is able to sense different force vectors, either parallel or perpendicular to the membrane. This provides a paradigm for proteins whose apparent uniform function is in fact achieved by a variety of distinct mechanisms involving different molecular architectures.

Description

Keywords

Actomyosin, Animals, Cell Adhesion, Cell Proliferation, Drosophila, Extracellular Matrix, Integrins, Protein Binding, Talin, Vinculin

Journal Title

Curr Biol

Conference Name

Journal ISSN

0960-9822
1879-0445

Volume Title

25

Publisher

Elsevier BV
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/L006669/1)
Wellcome Trust (086451/Z/08/Z)
Biotechnology and Biological Sciences Research Council (BB/D526102/1)
Wellcome Trust (069943/Z/02/Z)
This work was supported by grants from the Wellcome Trust (069943 and 086451) and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/L006669/1) to N.H.B., a BBSRC studentship to J.W. (BB/D526102/1), and a grant from the Royal Society and Medical Research Council (MR/K015664/1) to M.P.