TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
06
09
2022
revised:
08
01
2023
accepted:
17
02
2023
entrez:
7
3
2023
pubmed:
8
3
2023
medline:
10
3
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36880935
pii: 213923
doi: 10.1083/jcb.202209010
pmc: PMC9997659
pii:
doi:
Substances chimiques
Talin
0
Adaptor Proteins, Signal Transducing
0
TLN1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : DRCRPG-May21\100002
Pays : United Kingdom
Informations de copyright
© 2023 Gallego-Paez et al.
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