Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that alpha-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that alpha-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in alpha-catenin conformation. We identified regions in the alpha-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant alpha-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for alpha-catenin mobility and the existence of an antibody recognizing alpha-catenin in a force-dependent manner further supported the notion that alpha-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/ncb2055 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Differential Expression of Proteins Involved in Skin Barrier Maintenance and Vitamin D Metabolism in Atopic Dermatitis: A Cross-Sectional, Exploratory Study.
Int J Mol Sci
December 2024
Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by proteins involved in skin barrier maintenance and vitamin D metabolism. Using an intra-patient design, this study compared protein expression in intra-lesional (IL) and peri-lesional (PL) skin biopsies from AD patients and examined associations between protein levels, vitamin D status, and clinical features. Forty-four biopsies from twenty-two AD patients were analyzed using antibody microarrays targeting twelve proteins.
View Article and Find Full Text PDFKlotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.
Int J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
View Article and Find Full Text PDFα-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.
J Cell Biol
March 2025
Department of Pulmonary Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.
View Article and Find Full Text PDFα-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak.
Biol Open
January 2025
Department of Pulmonary Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Epithelial cell cohesion and barrier function critically depend on α-catenin, an actin-binding protein and essential constituent of cadherin-catenin-based adherens junctions. α-catenin undergoes actomyosin force-dependent unfolding of both actin-binding and middle domains to strongly engage actin filaments and its various effectors; this mechanosensitivity is critical for adherens junction function. We previously showed that α-catenin is highly phosphorylated in an unstructured region that links the mechanosensitive middle and actin-binding domains (known as the P-linker region), but the cellular processes that promote α-catenin phosphorylation have remained elusive.
View Article and Find Full Text PDFLow-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.
Acta Pharmacol Sin
January 2025
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Pressure overload induces pathological cardiac remodeling, including cardiac hypertrophy and fibrosis, resulting in cardiac dysfunction or heart failure. Recently, we observed that the low-density lipoprotein receptor-related protein 6 (LRP6), has shown potential in enhancing cardiac function by mitigating cardiac fibrosis in a mouse model subjected to pressure overload. In this study, we investigated the role of LRP6 as a potential modulator of pressure overload-induced cardiac hypertrophy and elucidated the underlying molecular mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!