The centrosomal protein FGFR1OP controls myosin function in murine intestinal epithelial cells.

Autor:	Trsan T; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Peng V; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Krishna C; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Ohara TE; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Beatty WL; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA., Sudan R; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Kanai M; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Krishnamoorthy P; Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA., Rodrigues PF; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Fachi JL; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Grajales-Reyes G; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Jaeger N; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Fitzpatrick JAJ; Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA; Departments of Cell Biology & Physiology and Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, USA., Cella M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Gilfillan S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Nakata T; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Jaiswal A; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Stappenbeck TS; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Daly MJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Xavier RJ; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: xavier@molbio.mgh.harvard.edu., Colonna M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mcolonna@wustl.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Sep 23; Vol. 59 (18), pp. 2460-2476.e10. Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1016/j.devcel.2024.06.001
Abstrakt:	Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. FGFR1OP insufficiency hindered epithelial resilience during colitis. FGFR1OP was crucial for preserving non-muscle myosin II activity, ensuring the integrity of the actomyosin cytoskeleton and crypt cell adhesion. This role of FGFR1OP suggests that its deficiency in genetically predisposed individuals may reduce epithelial renewal capacity, heightening susceptibility to inflammation and disease. Competing Interests: Declaration of interests R.J.X. is co-founder of Jnana Therapeutics and Celsius Therapeutics, scientific advisory board member at Nestlé, and board director at MoonLake Immunotherapeutics. These organizations had no roles in this study. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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