Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing. Focal adhesions are multifunctional organelles that mediate cell-ECM adhesion, force transmission, cytoskeletal regulation and signalling. Focal adhesions consist of a complex network of trans-plasma-membrane integrins and cytoplasmic proteins that form a <200-nm plaque linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine. However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photoactivated localization microscopy) to map nanoscale protein organization in focal adhesions. Our results reveal that integrins and actin are vertically separated by a ∼40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signalling layer containing integrin cytoplasmic tails, focal adhesion kinase and paxillin; an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein and α-actinin. By localizing amino- and carboxy-terminally tagged talins, we reveal talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. The composite multilaminar protein architecture provides a molecular blueprint for understanding focal adhesion functions.
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http://dx.doi.org/10.1038/nature09621 | DOI Listing |
J Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Fundação de Medicina Tropical - Dr Heitor Vieira Dourado, Manaus, AM, Brazil; Universidade Nilton Lins, Manaus, AM, Brazil. Electronic address:
Snake venom galactoside-binding lectins (SVgalLs) comprise a group of toxins with the ability to bind specifically, reversibly, and non-covalently to galactose-containing carbohydrates in a Ca-dependent manner. Several SVgalLs have been identified and isolated from Bothrops snake venoms, presenting highly similar structures and biological functions. BjcuL is a galactoside binding C-type lectin isolated from the venom of South America Bothrops jararacussu and consists of the most investigated lectin.
View Article and Find Full Text PDFJ Control Release
January 2025
School of Medicine, Chongqing University, 131 Yubei Street, Shapingba District, Chongqing 400044, China. Electronic address:
Aging is a critical factor in the onset and progression of neurodegenerative diseases and cognitive decline, with aging-related neuroinflammation and cellular senescence being major contributors. In the aging brain, the cerebral vascular endothelium overexpresses vascular cell adhesion molecule 1 (VCAM1), activating microglia and leading to neuroinflammation and cognitive impairment. Quercetin, a natural neuroprotective agent widely used for treating neurodegenerative diseases, their therapeutic efficacy, however, is limited by its poor water solubility and inability to penetrate the blood-brain barrier (BBB).
View Article and Find Full Text PDFActa Biomater
January 2025
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. Electronic address:
Hydrogels composed of collagen, the most abundant protein in the human body, are widely used as scaffolds for tissue engineering due to their ability to support cellular activity. However, collagen hydrogels with encapsulated cells often experience bulk contraction due to cell-generated forces, and conventional strategies to mitigate this undesired deformation often compromise either the fibrillar microstructure or cytocompatibility of the collagen. To support the spreading of encapsulated cells while preserving the structural integrity of the gels, we present an interpenetrating network (IPN) of two distinct collagen networks with different crosslinking mechanisms and microstructures.
View Article and Find Full Text PDFInt J Food Microbiol
January 2025
College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
Yersinia intermedia, Y. frederiksenii, and Y. kristensenii are a group of pathogens that are commonly found in food and are often overlooked in terms of their pathogenic potential.
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