The actin binding sites of talin have both distinct and complementary roles in cell-ECM adhesion

Abstract

Cell adhesion requires linkage of transmembrane receptors to the cytoskeleton through intermediary linker proteins. Integrin-based adhesion to the extracellular matrix (ECM) involves large adhesion complexes that contain multiple cytoskeletal adapters that connect to the actin cytoskeleton. Many of these adapters, including the essential cytoskeletal linker Talin, have been shown to contain multiple actin-binding sites (ABSs) within a single protein. To investigate the possible role of having such a variety of ways of linking integrins to the cytoskeleton, we generated mutations in multiple actin binding sites in Drosophila talin. Using this approach, we have been able to show that different actin-binding sites in talin have both unique and complementary roles in integrin-mediated adhesion. Specifically, mutations in either the C-terminal ABS3 or the centrally located ABS2 result in lethality showing that they have unique and non-redundant function in some contexts. On the other hand, flies simultaneously expressing both the ABS2 and ABS3 mutants exhibit a milder phenotype than either mutant by itself, suggesting overlap in function in other contexts. Detailed phenotypic analysis of ABS mutants elucidated the unique roles of the talin ABSs during embryonic development as well as provided support for the hypothesis that talin acts as a dimer in in vivo contexts. Overall, our work highlights how the ability of adhesion complexes to link to the cytoskeleton in multiple ways provides redundancy, and consequently robustness, but also allows a capacity for functional specialization.

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

“…Biochemical components allow cd-ECMs to anchor transmembrane receptors, such as integrins and other non-canonical receptors, to interact with cells [ 129 ]. These cell surface receptors connect the bioactive components of ECMs to the cytoskeleton and activate a series of intracellular signaling pathways, which plays a vital role in mediating cell adhesion, proliferation, migration, differentiation, and homing [ 130 , 131 ]. Moreover, cd-ECMs provide bind sites for various growth factors to modulate their bioavailability to achieve regulatory effects.…”