更新于：2024-09-19

FERMT2

更新于：2024-09-19

基本信息

别名

FERM domain containing kindlin 2、Fermitin family homolog 2、FERMT2

+ [9]

简介

Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.

关联

100 项与 FERMT2 相关的临床结果

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100 项与 FERMT2 相关的转化医学

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0 项与 FERMT2 相关的专利（医药）

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439

项与 FERMT2 相关的文献（医药）

2024-09-01·Biochemistry and Biophysics Reports

Actin-organizing protein palladin modulates C2C12 cell fate determination

Article

作者: Nguyen, Ngoc Uyen Nhi ; Hsu, Ching-Cheng ; Ali, Shah R ; Wang, Hao-Ven

BackgroundCell confluency and serum deprivation promote the transition of C2C12 myoblasts into myocytes and subsequence fusion into myotubes. However, despite all myoblasts undergoing the same serum deprivation trigger, their responses vary: whether they become founder myocytes, remain proliferative, or evolve into fusion-competent myocytes remains unclear. We have previously shown that depletion of the scaffolding protein palladin in myoblasts inhibits cell migration and promotes premature muscle differentiation, pointing to its potential significance in muscle development and the necessity for a more in-depth examination of its function in cellular heterogeneity.Methods and resultsHere, we showed that the subcellular localization of palladin might contribute to founder-fate cell decision in the early differentiation process. Depleting palladin in C2C12 myoblasts depleted integrin-β3 plasma membrane localization of and focal adhesion formation at the early stage of myogenesis, decreased kindlin-2 and metavinculin expression during the myotube maturation process, leading to the inability of myocytes to fuse into preexisting mature myotubes. This aligns with previous findings where early differentiation into nascent myotubes occurred but compromised maturation. In contrast, wildtype C2C12 overexpressing the 140-kDa palladin isoform developed a polarized morphology with star-like structures toward other myoblasts. However, this behaviour was not observed in palladin-depleted cells, where the 140-kDa palladin overexpression could not recover cell migration capacity, suggesting other palladin isoforms are also needed to establish cell polarity.ConclusionOur study identifies a counter-intuitive role for palladin in regulating myoblast-to-myocyte cell fate decisions and impacting their ability to form mature multinucleated myotubes by influencing cell signalling pathways and cytoskeletal organization, necessary for skeletal muscle regeneration and repair studies.

2024-09-01·Cellular Signalling

Kindlin-2 mediates Peyronie's disease through activation of TGF-β/Smad signaling pathway under the presence of TGF-β1

Article

作者: Shan, Jiahao ; Wu, Jitao ; Cui, Yuanshan ; Yang, Xiaobo ; Cai, Tong

BACKGROUNDPeyronie's disease (PD) causes benign plaques or induration in tunica albuginea (TA). Kindlin-2 regulates the TGF-β1/Smad3 pathway, which accelerates kidney fibrosis. The study is aimed mainly to investigate the impact of Kindlin-2 on PD formation and its signaling pathways, notably the TGF-β/Smad pathway in the presence of TGF-β1.METHODSIn this mouse investigation, adenovirus TGF-β1 was injected into TA to produce PD. The model was successfully induced 45 days later. Western Blot (WB) and immunohistochemistry (IHC) were utilized to measure Kindlin-2 in PD model tissue. WB and immunofluorescence assays were utilized to confirm the impact of TGF-β1 on Kindlin-2 levels in vitro. The interaction among Kindlin-2, TβRI, and Smad3 was detected using immunoprecipitation (IP) experiments. We examined how TGF-β1 affects Smad3 phosphorylation and downstream gene activation process. Finally, Kindlin-2 and the level of tissue fibrosis were examined in PD model.RESULTSKindlin-2 levels were elevated in the TGF-β1-induced PD model, confirming that TGF-β1 can increase Kindlin-2 levels in primary PD cells. Moreover, Kindlin-2 mediates Smad3-TβRI interaction, activates p-Smad3, and enhances TGF-β1 target gene expression. In vivo investigations reveal that Kindlin-2 promotes PD development and tissue fibrosis. The regulatory effects of Kindlin-2 need the presence of TGF-β1. Tissue fibrosis can be reduced by downregulating Kindlin-2.CONCLUSIONKindlin-2 does not directly activate Smad3 to induce tissue fibrosis. Instead, it exerts its effect through the combined influence of TGF-β1. Inhibiting Kindlin-2 could potentially be a treatment for PD.

2024-06-01·iScience

Acetyl-NPKY of integrin-β1 binds KINDLIN2 to control endothelial cell proliferation and junctional integrity

Article

作者: Sidibé, Adama ; Zhang, Pingfeng ; Mykuliak, Vasyl V ; Wu, Jinhua ; Wehrle-Haller, Bernhard ; Hytönen, Vesa P

Integrin-dependent crosstalk between cell-matrix adhesions and cell-cell junctions is critical for controlling endothelial permeability and proliferation in cancer and inflammatory diseases but remains poorly understood. Here, we investigated how acetylation of the distal NPKY-motif of Integrin-β1 influences endothelial cell physiology and barrier function. Expression of an acetylation-mimetic β1-K794Q-GFP mutant led to the accumulation of immature cell-matrix adhesions accompanied by a transcriptomic reprograming of endothelial cells, involving genes associated with cell adhesion, proliferation, polarity, and barrier function. β1-K794Q-GFP induced constitutive MAPK signaling, junctional impairment, proliferation, and reduced contact inhibition at confluence. Structural analysis of Integrin-β1 interaction with KINDLIN2, biochemical pulldown assay, and binding energy determination by using molecular dynamics simulation showed that acetylation of K794 and the K794Q-mutant increased KINDLIN2 binding affinity to the Integrin-β1. Thus, enhanced recruitment of KINDLIN2 to Lysine-acetylated Integrin-β1 and resulting modulation of barrier function, offers new therapeutic possibilities for controlling vascular permeability and disease conditions.