Role of Signal-Regulated Changes in Microtubule Stability Dynamics through <i>α</i>-Tubulin Phosphorylation on Ser/Tyr in Modulation of Salivary Gland Matrix Metalloproteinase-9 (MMP-9) Secretion in Response to <i>Porphyromonas gingivalis</i>and Ghrelin

• 作者: Amalia Slomiany Bronislaw L. Slomiany
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: P. gingivalis Oral Mucosa GHRELIN MMP-9 α-Tubulin Ser/Tyr PHOSPHORYLATION
• 年，卷（期）: 2017,（2）
• 页码范围: 22-38
• 页数: 17页
• 分类号: R73

摘要

Up-regulation in salivary gland acinar cell MMP-9 secretion in response to proinflammatory challenge by periodontopathic bacterium, P. gingivalis relays heavily on the factors that influence the protein processing at the level of endoplasmic reticulum-to-Golgi trafficking, and occurs in concert with the changes in the stability dynamics of the major cytoskeleton polymeric structures, microtubules (MTs). In this study, we report that P. gingivalis LPS-elicited induction in the acinar cell MMP-9 secretion is accompanied by the enhancement in MT stabilization, while the modulatory influence of peptide hormone, ghrelin, is associated with MT destabilization. Further, we reveal that the changes in MT dynamics induced by the LPS and ghrelin occur through signal-regulated α-tubulin phosphorylation on Ser/Tyr. The LPS effect is reflected in a marked increase in PKCδ-mediated α-tubulin phosphorylation on Ser, whereas the modulatory influence of ghrelin on MT dynamics is manifested in by SFK-dependent phosphorylation of α-tubulin on Tyr. Moreover, we show that that the changes in MT dynamics, conferred by the LPS and ghrelin, affect the Golgi localization of GTP-Arf1 and the recruitment and activation of PKD2. The findings underscore the role of signal-regulated changes in MT stability dynamics through PKCδ/SFK-mediated α-tubulin phosphorylation on Ser/Tyr in controlling the salivary gland acinar cell MMP-9 secretion in response to P. gingivalis LPS as well as its modulation by ghrelin.