The Centrosome Undergoes Plk1-Independent Interphase Maturation during Inflammation and Mediates Cytokine Release

Anastassiia Vertii, Maria Ivshina, Wendy Zimmerman, Heidi Hehnly, Shashi Kant, Stephen Doxsey

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)377-386
Number of pages10
JournalDevelopmental Cell
Volume37
Issue number4
DOIs
StatePublished - May 23 2016
Externally publishedYes

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Keywords

  • Centrosome
  • Cytokines
  • LPS
  • Microtubules
  • Recycling endosomes

ASJC Scopus subject areas

  • Developmental Biology

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