The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering

Ellis, Stephanie J. and Lostchuck, Emily and Goult, Benjamin T. and Bouaouina, Mohamed and Fairchild, Michael J. and López-Ceballos, Pablo and Calderwood, David A. and Tanentzapf, Guy (2014) The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering. PLoS Genetics, 10 (11). e1004756. ISSN 1553-7404. (doi:https://doi.org/10.1371/journal.pgen.1004756) (Full text available)

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Abstract

Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 13 Nov 2014 20:28 UTC
Last Modified: 27 Jun 2017 22:53 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/44544 (The current URI for this page, for reference purposes)
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