The dynamic organization of actin cytoskeleton meshworks relies on multiple actin-binding proteins endowed with distinct actin-remodeling activities. Filamin A is a large multi-domain scaffolding protein that cross-links actin filaments with orthogonal orientation in response to various stimuli. As such it plays key roles in the modulation of cell shape, cell motility, and differentiation throughout development and adult life. The essentiality and complexity of Filamin A is highlighted by mutations that lead to a variety of severe human disorders affecting multiple organs. One of the most conserved activity of Filamin A is to bridge the actin cytoskeleton to integrins, thereby maintaining the later in an inactive state. We here review the numerous mechanisms cells have developed to adjust Filamin A content and activity and focus on the function of Filamin A as a gatekeeper to integrin activation and associated adhesion and motility.
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http://dx.doi.org/10.3389/fcell.2020.591323 | DOI Listing |
J Mol Biol
January 2025
Department of Applied Bioscience, Kanazawa Institute of Technology. Electronic address:
A variety of potential biological roles of mechanical forces have been proposed in the field of cell biology. In particular, mechanical forces alter the mechanical conditions within cells and their environment, exerting a strong effect on the reorganization of the actin cytoskeleton. Single-molecule imaging studies have provided evidence that an actin filament may act as a mechanosensor.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Division of Hemostasis and Thrombosis, Department of Medicine, BIDMC, Harvard Medical School, Boston, MA, USA.
The actin cytoskeleton serves an important, but poorly characterized, role in controlling granule exocytosis. The dynamic nature of actin remodeling allows it to act both as a barrier to prevent indiscriminate granule release and as a facilitator of membrane fusion. In its capacity to promote exocytosis, filamentous actin binds to components of the exocytotic machinery through actin binding proteins, but also through direct interactions with SNAREs.
View Article and Find Full Text PDFIn addition to regulating the actin cytoskeleton, Cofilin also senses and responds to environmental stress. Cofilin can promote cell survival or death depending on context. Yet, many aspects of Cofilin's role in survival need clarification.
View Article and Find Full Text PDFAnim Cells Syst (Seoul)
January 2025
School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
βPix is a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, which play important roles in dendritic spine morphogenesis by modulating actin cytoskeleton organization. The formation and plasticity of the dendritic spines are essential for normal brain function. Among the alternatively spliced βPix isoforms, βPix-b and βPix-d are expressed specifically in neurons.
View Article and Find Full Text PDFStem cells adapt to their local mechanical environment by rearranging their cytoskeleton, which underpins the evolution of their shape and fate as well as the emergence of tissue structure and function. Here, in the second part of a two-part experimental series, we aimed to elucidate spatiotemporal cytoskeletal remodeling and resulting changes in morphology and mechanical properties of cells and their nuclei. Akin to mechanical testing of the most basic living and adapting unit of life, i.
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