| 1997 |
The conserved C-terminal I/LWEQ module (last ~197 amino acids) of vertebrate talin (TLN1) is an F-actin binding domain; the corresponding domain from yeast Sla2 also binds F-actin in vitro, and mutation of a conserved residue in the fourth block abolishes this interaction, defining the I/LWEQ module as a new actin-binding motif. |
In vitro F-actin competition binding assay, site-directed mutagenesis, sequence analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9159132
|
| 1999 |
The I/LWEQ modules from all four major groups (metazoan talin, Dictyostelium TalA/B, metazoan Hip1, yeast Sla2) bind F-actin in vitro, and GFP-fusion proteins of the I/LWEQ modules of talin and Sla2 bind F-actin in vivo, confirming the I/LWEQ module as a conserved actin-binding motif linking diverse proteins to the actin cytoskeleton. |
In vitro F-actin binding assay, GFP-fusion localization in cells |
Biochemical and biophysical research communications |
High |
10581178
|
| 1999 |
The human TLN1 gene spans more than 23 kb, consists of 57 exons, and maps to chromosome band 9p13; Northern blot analysis showed TLN expression in diverse human tissues including leukocytes, lung, placenta, liver, kidney, spleen, thymus, colon, skeletal muscle, and heart. |
BAC clone isolation, FISH, radiation hybrid mapping, Northern blot |
Genomics |
Medium |
10610730
|
| 2002 |
The talin head domain F3 subdomain (PTB-like) binds the integrin β3 cytoplasmic tail with higher affinity than F2 and activates integrin αIIbβ3 when expressed in cells; this interaction depends on NPXY motifs in the integrin β tail, establishing that talin activates integrins through a PTB domain–like mechanism. |
Binding assays with isolated subdomains, cell-based integrin activation assay, molecular modeling, mutagenesis |
The Journal of biological chemistry |
High |
11932255
|
| 2002 |
Type I phosphatidylinositol phosphate kinase isoform-γ661 (PIPKIγ661) is targeted to focal adhesions through direct association with talin; PIPKIγ661 is tyrosine-phosphorylated by FAK signaling, which increases both its kinase activity and its association with talin, defining a mechanism for spatially restricted PtdIns(4,5)P2 generation at focal adhesions. |
Co-immunoprecipitation, subcellular fractionation, in vitro kinase assay, FAK mutant cells |
Nature |
High |
12422220
|
| 2003 |
Multiple phosphotyrosine-binding (PTB) domain-containing proteins (including talin, ICAP1-α, Numb, Dok-1) bind integrin β cytoplasmic tails via a canonical PTB domain–NPXY ligand interaction; integrin class-specific interactions were demonstrated, confirming talin's PTB-like F3 subdomain as a conserved integrin-tail binding module. |
Recombinant PTB domain binding assays, co-immunoprecipitation, NPXY mutagenesis, gain/loss-of-function mutations |
Proceedings of the National Academy of Sciences of the United States of America |
High |
12606711
|
| 2004 |
The actin-binding activity of Talin1 (and Talin2, Hip1, Hip12) within the I/LWEQ module is regulated by intrasteric inhibition: a structural element upstream of the I/LWEQ module occludes the primary actin-binding determinants. The I/LWEQ module also contains a dimerization motif and stabilizes actin filaments against depolymerization. |
In vitro F-actin cosedimentation assay, binding affinity measurements, truncation analysis |
Biochemistry |
High |
15581353
|
| 1995 |
Focal adhesion kinase (FAK) physically associates with talin (TLN1) in NIH 3T3 cells; a 48-amino acid sequence in the FAK C-terminal domain mediates talin binding in vitro, and integrin-induced FAK phosphorylation correlates with integrin's ability to bind talin, suggesting talin mediates FAK activation downstream of integrins. |
Co-immunoprecipitation, in vitro binding assay with FAK deletion mutants, integrin mutant analysis |
The Journal of biological chemistry |
High |
7622520
|
| 2006 |
The I/LWEQ module at the C-terminus of Talin1 is necessary and sufficient for targeting to focal adhesion complexes in vivo; this focal adhesion targeting function correlates with but is separable from actin binding, and is regulated by an intrasteric interaction with an upstream α-helix that masks both the actin-binding and adhesion-targeting elements in full-length Talin1. |
GFP-fusion truncation constructs, live-cell imaging, site-directed mutagenesis |
Cell motility and the cytoskeleton |
High |
16830345
|
| 2007 |
The C-terminal dimerization motif (a putative coiled coil) within the Talin1 I/LWEQ module is required for F-actin binding, actin filament stabilization, actin filament cross-linking, and focal adhesion targeting; alanine-scanning mutagenesis of this coiled coil abolishes all these activities, demonstrating that dimerization is essential for Talin1 function at focal adhesions. |
Alanine-scanning mutagenesis, in vitro F-actin cosedimentation, GFP-fusion focal adhesion targeting assay |
Biochemistry |
High |
17722883
|
| 2007 |
Vinculin directly interacts with talin (TLN1) to regulate focal adhesion formation; the vinculin head (binding talin) controls integrin dynamics and clustering while the vinculin tail links focal adhesions to the actin force machinery; expression of vinculin constructs with unmasked binding sites induces dramatic focal adhesion growth via direct talin interaction. |
Vinculin mutant expression, FRAP, co-immunoprecipitation, quantitative FA analysis |
The Journal of cell biology |
High |
18056416
|
| 2013 |
TLN1 loss-of-function (shRNA knockdown) significantly enhances docetaxel chemosensitivity specifically in triple-negative breast cancer (TNBC) cell lines but not in hormone receptor-positive or normal mammary epithelial cells; TLN1-deficient xenografts show reduced tumor mass after chemotherapy, establishing TLN1 as a modulator of chemotherapy response in TNBC. |
shRNA RNAi screen, cell viability assays in multiple cell lines, mouse xenograft model |
Clinical cancer research |
Medium |
23479679
|
| 2013 |
TLN1 is a direct target of miR-9 in ovarian serous carcinoma cells; TLN1 knockdown mimics miR-9 overexpression (inhibiting proliferation, migration, invasion), and TLN1 modulates the FAK/AKT signaling pathway, which is inhibited by increased miR-9 levels. |
Luciferase reporter assay (3'UTR targeting), siRNA knockdown, miRNA transfection, Western blot for FAK/AKT pathway |
International journal of molecular medicine |
Medium |
23722670
|
| 2021 |
TLN1 and FAK form a functional axis (Cdk5/Tln1/FAK) required for cancer cell trans-endothelial migration (TEM) and extravasation; the structural (not phosphorylation-dependent) functions of FAK and Tln1 are required for invadopodia formation and vascular breaching; inhibition of FAKS732 phosphorylation delocalizes ERK from the nucleus and decreases ERK phosphorylation. |
3D microfluidic vascular model, siRNA knockdown, chemical inhibition, in vivo lung colonization assay, immunofluorescence, Western blot |
Biomaterials |
Medium |
34333365
|
| 2022 |
TLN1 interacts with integrin β1 (ITGB1) at focal adhesions; silencing TLN1 in TNBC cells attenuates migration by interfering with dynamic focal adhesion formation and regulates the FAK-AKT signaling pathway and epithelial-mesenchymal transition; a small molecule C67399 blocking the TLN1–integrin β1 binding interface suppresses TNBC metastasis in xenograft models. |
Western blot, RT-PCR, co-immunoprecipitation, computational drug screening targeting protein-protein interface, xenograft assay, siRNA knockdown |
eLife |
Medium |
35285795
|
| 2023 |
TLN1 contains a cancer-enriched alternatively spliced exon (exon 17b, 51 nt) inserted between exons 17 and 18 that introduces 17 amino acids between the R1 and R2 force-dependent switch domains; this lowers the force required to open R1-R2 switches, enhances vinculin binding, and alters cell adhesion dynamics and motility; TGF-β/SMAD3 signaling regulates this isoform switch. |
Alternative splicing analysis, single-molecule force spectroscopy (magnetic tweezers), biochemical vinculin binding assay, live-cell adhesion/motility imaging, TGF-β/SMAD3 pathway manipulation |
The Journal of cell biology |
High |
36880935
|
| 2023 |
In C. elegans, TLN-1 W387A (CRISPR-generated allele predicted to disrupt integrin binding) produces only mild motility and ovulation defects without disrupting actin cytoskeleton architecture in body wall muscles or gonadal sheath, suggesting that W387 plays a minor role in integrin binding in vivo. |
CRISPR allele generation, behavioral assays, fluorescence microscopy of actin cytoskeleton |
microPublication biology |
Medium |
36685729
|
| 2023 |
TLN1 overexpression in cardiac microvascular endothelial cells (CMVECs) upregulates integrin alpha 5 (ITGA5), and ITGA5 knockdown reverses the protective effects of TLN1 overexpression against ox-LDL-induced dysfunction, establishing a TLN1→ITGA5 axis in endothelial cell adhesion and survival. |
Overexpression and siRNA knockdown in CMVECs, CCK-8 proliferation assay, flow cytometry apoptosis, angiogenesis assay, Western blot |
Folia morphologica |
Low |
37144848
|
| 2025 |
FLI1 and GATA1 cooperatively regulate TLN1 transcription through an intronic FLI1-binding region; FLI1 germline variants associated with bleeding disorders show reduced cooperative transcriptional activity, resulting in up to 88% reduction in talin-1 protein levels in patient platelets, contributing to platelet dysfunction. |
scRNA-seq, luciferase reporter assay, ChIP-seq analysis, Western blot of patient platelets, FLI1 variant characterization |
Haematologica |
High |
39744817
|
| 2025 |
EMP1 competes with SMURF1 for the TLN1 binding site, thereby inhibiting SMURF1-mediated ubiquitination and degradation of TLN1; accumulated TLN1 promotes FAK phosphorylation, establishing an EMP1/TLN1/FAK pro-inflammatory signaling axis that drives hepatic stellate cell activation; EMP1 silencing suppresses this post-translational cascade. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, Western blot, rodent MASLD-IRI model, human sample validation |
Molecular biomedicine |
Medium |
41284206
|
| 2025 |
RAP1 GTPase regulates platelet aggregation by direct interaction with TALIN-1 (Tln-1) to control αIIbβ3 integrin activation; mice with impaired RAP1–Tln-1 interaction (Tln-1 mR35/118E) show a milder defect in phosphatidylserine exposure than complete Rap1 knockout, and ROCK inhibition fully restores PtdSer exposure in Tln-1 mR35/118E platelets, establishing that RAP1 regulates procoagulant activity through both Tln-1-dependent (integrin) and -independent (RHOA) pathways. |
Knock-in mouse model (Tln-1 mR35/118E), flow cytometry for PtdSer exposure, ROCK inhibitor pharmacology, in vitro and in vivo coagulation assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.22.655614
|
| 2024 |
LAYN (layilin) interacts with TLN1 (validated by co-immunoprecipitation), and CREB1 binds the LAYN promoter to transcriptionally upregulate LAYN; the resulting CREB1→LAYN→TLN1→integrin β1 (ITGB1) signaling axis promotes cholangiocarcinoma metastasis by activating c-Jun, p38 MAPK, and ERK phosphorylation. |
Co-immunoprecipitation, ChIP, luciferase reporter, overexpression/knockdown, Western blot, in vivo metastasis model |
Heliyon |
Medium |
39286102
|