Skip to main content
Kent Academic Repository

TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity

Gallego-Paez, LM, Edwards, WJS, Chanduri, M, Guo, Yanyu, Koorman, T, Lee, C-Y, Grexa, N, Derksen, PWB, Yan, Jie, Schwartz, Martin A., and others. (2023) TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. Journal of Cell Biology, 222 (5). Article Number e202209010. ISSN 0021-9525. E-ISSN 1540-8140. (doi:10.1083/jcb.202209010) (KAR id:96773)


Talin-1 is the core mechanosensitive adapter protein linking integrins to the cytoskeleton. The TLN1 gene is comprised of 57 exons that encode the 2,541 amino acid TLN1 protein. TLN1 was previously considered to be expressed as a single isoform. However, through differential pre-mRNA splicing analysis, we discovered a cancer-enriched, non-annotated 51-nucleotide exon in TLN1 between exons 17 and 18, which we refer to as exon 17b. TLN1 is comprised of an N-terminal FERM domain, linked to 13 force-dependent switch domains, R1-R13. Inclusion of exon 17b introduces an in-frame insertion of 17 amino acids immediately after Gln665 in the region between R1 and R2 which lowers the force required to open the R1-R2 switches potentially altering downstream mechanotransduction. Biochemical analysis of this isoform revealed enhanced vinculin binding, and cells expressing this variant show altered adhesion dynamics and motility. Finally, we showed that the TGF-β/SMAD3 signaling pathway regulates this isoform switch. Future studies will need to consider the balance of these two TLN1 isoforms.

Item Type: Article
DOI/Identification number: 10.1083/jcb.202209010
Additional information: For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Uncontrolled keywords: talin, integrin, splicing, splice variant, TLN1, CLSTN1, mechanotransduction, TGF-b
Subjects: Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Cancer Research UK (
Biotechnology and Biological Sciences Research Council (
Depositing User: Ben Goult
Date Deposited: 07 Sep 2022 14:43 UTC
Last Modified: 11 Mar 2024 15:06 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.