L-Plastin promotes podosome longevity and supports macrophage motility.

Autor: Zhou JY; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Szasz TP; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Stewart-Hutchinson PJ; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Sivapalan J; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Todd EM; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Deady LE; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States., Cooper JA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, United States., Onken MD; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, United States., Morley SC; Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States; Department of Pathology and Immunology, Division of Immunobiology, Washington University School of Medicine, St. Louis, MO, 63110, United States. Electronic address: morley_c@kids.wustl.edu.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2016 Oct; Vol. 78, pp. 79-88. Date of Electronic Publication: 2016 Sep 07.
DOI: 10.1016/j.molimm.2016.08.012
Abstrakt: Elucidating the molecular regulation of macrophage migration is essential for understanding the pathophysiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL -/- mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP + mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL -/- mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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