title: The Centrosome Undergoes Plk1-Independent Interphase Maturation during Inflammation and Mediates Cytokine Release.
abstract: Cytokine production is a necessary event in the immune response during inflammation and is associated with mortality during sepsis, autoimmune disorders, cancer, and diabetes. Stress-activated MAP kinase signaling cascades that mediate cytokine synthesis are well established. However, the downstream fate of cytokines before they are secreted remains elusive. We report that pro-inflammatory stimuli lead to recruitment of pericentriolar material, specifically pericentrin and γ-tubulin, to the centrosome. This is accompanied by enhanced microtubule nucleation and enrichment of the recycling endosome component FIP3, all of which are hallmarks of centrosome maturation during mitosis. Intriguingly, centrosome maturation occurs during interphase in an MLK-dependent manner, independent of the classic mitotic kinase, Plk1. Centrosome disruption by chemical prevention of centriole assembly or genetic ablation of pericentrin attenuated interleukin-6, interleukin-10, and MCP1 secretion, suggesting that the centrosome is critical for cytokine production. Our results reveal a function of the centrosome in innate immunity.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: anastassiia.vertii@umassmed.edu.
authors.forename: Anastassiia
authors.initials: A
authors.lastname: Vertii
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ivshina
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Zimmerman
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hehnly
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Kant
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: stephen.doxsey@umassmed.edu.
authors.forename: Stephen
authors.initials: S
authors.lastname: Doxsey
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000187:drug effects / Q000378:metabolism; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology*; D007399:Interphase; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000941:Antigens; D018797:Cell Cycle Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014404:Tubulin; D000097869:Polo-Like Kinase 1; C086178:pericentrin
keywords: LPS; centrosome; cytokines; microtubules; recycling endosomes