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Abstract
Allergic asthma is characterized by airway smooth muscle layer thickening, which is largely attributed to cell division that requires the formation of centrosomes. Centrosomes play a pivotal role in regulating bipolar spindle formation and cell division. Before mitosis, centrosomes undergo maturation characterized by expansion of pericentriolar material proteins, which facilitates spindle formation and mitotic efficiency of many cell types. Although polo-like kinase 1 (Plk1) has been implicated in centrosome maturation, the mechanisms by which Plk1 regulates the cellular process are incompletely elucidated. Here, we identified paxillin as a new Plk1-interacting protein in human airway smooth muscle cells. We unexpectedly found that phosphorylated paxillin (Ser-272) was localized in centrosomes of human smooth muscle cells, which regulated centrosome maturation and spindle assembly. Plk1 knockdown inhibited paxillin Ser-272 phosphorylation, centrosome maturation, and cell division. Furthermore, exposure to allergens enhanced airway smooth muscle layer and paxillin phosphorylation at this residue in mice, which was reduced by smooth muscle conditional knockout of Plk1. These findings suggest that Plk1 regulates centrosome maturation and cell division in part by modulating paxillin phosphorylation on Ser-272. Furthermore, Plk1 contributes to the pathogenesis of allergen-induced thickening of the airway smooth muscle layer by affecting paxillin phosphorylation at this position.
Highlights
Www.nature.com/scientificreports promotes centrosome maturation during mitosis[4,5,7,8]
Because centrosome maturation is important for bipolar spindle assembly of somatic cells[4,5], we evaluated the effects of paxillin KD on the cellular localization of PCNT and γ-tubulin which has a role in nucleation and polar orientation of microtubules during maturation[4,5,7,8]
The results suggest that Plk[1] regulates centrosomal maturation by controlling paxillin Ser-272 phosphorylation during mitosis of smooth muscle cells
Summary
Www.nature.com/scientificreports promotes centrosome maturation during mitosis[4,5,7,8]. Plk[1] may regulate other proteins during centrosome maturation. Paxillin is an actin-associated protein that has been implicated in focal adhesion formation, cell adhesion, migration, survival, and smooth muscle contraction[2,15,16,17,18]. Rodent paxillin undergoes phosphorylation at Ser-273 (equivalent to human paxillin Ser-272, NCBI Accession number, NP_002850.2) during migration of CHO-K1 cells, which regulates adhesion dynamics[19]. Paxillin gets phosphorylated at Tyr-31 and Tyr-118 during adhesion, migration, and contraction[2,15,17,20]. We identify paxillin as one of the major proteins complexing with Plk[1] in human airway smooth muscle (HASM) cells. Phosphorylated paxillin (Ser-272) mediated by Plk[1] is localized in centrosomes, which regulates centrosome maturation, spindle formation, and cell division. Plk[1] contributes to the progression of airway smooth muscle layer thickening in mice exposed to allergens
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