The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering.

Ellis, Stephanie J ORCID: 0000-0003-3341-3453, Lostchuck, Emily, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Bouaouina, Mohamed, Fairchild, Michael J ORCID: 0000-0001-6494-5140, López-Ceballos, Pablo, Calderwood, David A ORCID: 0000-0002-0791-4142 and Tanentzapf, Guy (2014) The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering. PLoS genetics, 10 (11). e1004756-.

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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
Uncontrolled Keywords:	Cell Membrane, Extracellular Matrix, Embryo, Nonmammalian, Animals, Drosophila melanogaster, Talin, Integrins, Fluorescence Recovery After Photobleaching, Cell Adhesion, Protein Structure, Tertiary, Embryonic Development, Point Mutation, Alleles
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:53
Last Modified:	13 Mar 2024 09:53
DOI:	10.1371/journal.pgen.1004756
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179324