The tale of two talins – two isoforms to fine‐tune integrin signalling

Abstract

Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

KANK2 Links αVβ5 Focal Adhesions to Microtubules and Regulates Sensitivity to Microtubule Poisons and Cell Migration

“…The question that arises is whether integrin αVβ5 FAs in MDA-MB-435S cells are the only ones linked to CMSCs through KANK2. Since the KANK localization to adhesions is primarily through talin (Gough and Goult, 2018) it is very likely that integrin αVβ3 FAs contain KANK2 as well. Our previously published results have shown that knockdown of either integrin β5 or β3 did not change cell migration, while knockdown using integrin αV-specific siRNA of both heterodimers αVβ3 and αVβ5, the only integrins containing αV expressed in MDA-MB-435S cells, dramatically inhibited migration.…”

“…The fate of such a complex depends on cell type, composition of ECM, matrix stiffness, integrin subtype, etc. ultimately leading to formation of a variety of IAC-induced structures including nascent adhesions, FAs, fibrillar adhesions, podosomes and invadopodia (Klapholz and Brown, 2017;Gough and Goult, 2018). Novel adhesive structures termed reticular adhesions (RAs) were identified in 2018, which are rich in integrin αvβ5 but devoid of most of the typical cytoskeletal components found in other IACs, and, instead, are connected to the clathrin machinery (Lock et al, 2018).…”

Definition of the fibroblast adhesome using multiplexed proximity biotinylation

“…The actinassociated baits BirA*-LPP, -TRIP6, -zyxin and -ponsin, and BirA*-vinculin, biotinylated peptides in the C-terminal R11 and R13/DD domains of talin, which lie proximal to the ABS3 actin-binding site 35 . Despite the many reported vinculin binding sites in talin, and localisation to multiple layers of IACs 15 , vinculin only biotinylated peptides at the C-terminus of talin 35 . No biotinylated peptides from B4 or B5 baits were found in the ABS1 or ABS2 domains of talin, despite their reported roles in actin binding [36][37][38] .…”

Talin Rod Domain Containing Protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation

“…Talin1 and 2 are cytoplasmic adapters that provide a direct mechanosensitive link between the integrin family of cell adhesion molecules and the actin cytoskeleton (Calderwood et al, 2013;Goult et al, 2018). Talins are comprised of an N-terminal atypical FERM domain (Elliott et al, 2010), coupled via a flexible linker to a large rod domain comprised of 63 helices arranged into 13 helical bundles, R1-R13 ( Fig.1A) (Goult et al, 2013;Gough and Goult, 2018). Twelve of the rod domains are arranged linearly, end-to-end to create the large extended talin rod domain which unfolds and stretches in response to mechanical force (Yao et al, 2016).…”