Alternative mechanisms for talin to mediate integrin function.
Alternative mechanisms for talin to mediate integrin function.
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DOI：
10.1016/j.cub.2015.01.043
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发表时间：
2015-03-30
期刊：
影响因子：
9.2
通讯作者：
Brown, Nicholas H.
中科院分区：
文献类型：
--
作者：
Klapholz, Benjamin;Herbert, Samantha L.;Wellmann, Jutta;Johnson, Robert;Parsons, Maddy;Brown, Nicholas H.
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. Integrin function requires distinct sets of talin domains in three different tissues Vinculin helps talin retain function when domains are removed Talin IBS2 is separated from integrins in muscle but not wing adhesion sites Vinculin and actomyosin contribute to separating IBS2 from integrins Klapholz et al. show that talin domains have variable importance in different developmental events in Drosophila, suggesting distinct mechanisms of action, with altered configurations of talin, vinculin, and integrins. These were validated by advanced imaging in vivo. Such diverse configurations may allow talin to sense a variety of forces.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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