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Review
. 2022 May;49(5):60.
doi: 10.3892/ijmm.2022.5116. Epub 2022 Mar 10.

Talin‑1 interaction network in cellular mechanotransduction (Review)

Ye Zhao  1 , Nikita Lykov  1 , Chimeng Tzeng  2
Affiliations
Review

Talin‑1 interaction network in cellular mechanotransduction (Review)

Ye Zhao et al. Int J Mol Med. 2022 May.

Abstract

The mechanical signals within the extracellular matrix (ECM) regulate cell growth, proliferation and differentiation, and integrins function as the hub between the ECM and cellular actin. Focal adhesions (FAs) are multi‑protein, integrin‑containing complexes, acting as tension‑sensing anchoring points that bond cells to the extracellular microenvironment. Talin‑1 serves as the central protein of FAs that participates in the activation of integrins and connects them with the actin cytoskeleton. As a cytoplasmic protein, Talin‑1 consists of a globular head domain and a long rod comprised of a series of α‑helical bundles. The unique structure of the Talin‑1 rod domain permits folding and unfolding in response to the mechanical stress, revealing various binding sites. Thus, conformation changes of the Talin‑1 rod domain enable the cell to convert mechanical signals into chemical through multiple signaling pathways. The present review discusses the binding partners of Talin‑1, their interactions, effects on the cellular processes, and their possible roles in diseases.

Keywords: Vinculin; deleted in liver cancer 1; mechanotransduction; ras‑associated protein 1; talin‑1; yes‑associated protein.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Activation of Talin-1 through interaction with Rap1 and PIP2. (A) Rap1 phosphorylation results in its activation, promoting the recruitment of Talin-1 to the plasma membrane. PIP2 interacts with Talin-1 F2 and F3 and induces the conformational change that reveals an integrin binding site in its F3 domain. (B) PIPKIγ co-localizes with Talin-1 F3, enzymatically promoting PIP2 production. (C) Fully activated, PIPKIγ-free Talin-1 binds and activates the integrin β subunit. Rap1, ras-proximate-1; PIP2, phosphatidylinositol-4,5-bisphosphate; PIPKIγ, type I phosphatidylinositol phosphate kinase γ.
Figure 2
Figure 2
Talin-1 interaction network in cellular mechanotransduction. (A) Kindlin is recruited to the plasma membrane via its interaction with membrane PIP2, reveals its autoinhibited conformation, binding to the integrin tail and promoting more stable active integrin conformation and enhanced ligand binding. The tail of the Kindlin recruits FAK via paxillin binding to its tail domain. Completely unfolded Talin-1 tail begins to interact with its various binding partners, R3 binds to the RIAM, and R8 interacts with DLC1, subsequently regulating the RhoA and paxillin activity. DLC1 and paxillin form a competitive interaction network, since both bind to the R8 domain. Talin-1 R13 binds to the actin. (B) With the exertion of medium intensity force, Talin-1 R3 unfolds, causing the dissociation of RIAM and exposure of the cryptic VBS, culminating in vinculin binding to unfolded R3, and actin binding to the vinculin tail. Increased protein levels of cytoskeleton-associated vinculin result in an increase in nuclear-localized YAP/TAZ levels. (C) In the presence of higher intensity force, unfolding of Talin-1 R8 causes the dissociation of DLC1 and promotes RhoA activity, consequently affecting the MLC-2 signaling pathway and YAP nuclear translocation. R3 domain unfolds completely at high intensity force and becomes a polypeptide chain that cannot bind vinculin. PIP2, phosphatidylinositol-4,5-bisphosphate; FAK, focal-adhesion kinase; RIAM, rap1-GTP interacting protein; DLC-1, deleted in liver cancer 1; RhoA, ras homolog family member A; VBS, vinculin binding site; YAP, yes-associated protein; TAZ, transcriptional coactivator with PDZ-binding motif; MLC-2, myosin light chain-2.
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Grants and funding

The present study was supported by a grant from National Natural Science Foundation of China (no. 31701279).