期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1866, 期 9, 页码 1463-1474出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2019.06.003
关键词
DRG2; GSK3 beta; Microtubule stability; Golgi fragmentation; Cell migration
资金
- National Research Foundation of Korea [NRF-2014R1A2A2A01005655, NRF-2014R1A6A1030318, NRF-2017R1D1A3B04030339, NRF-2018R1D1A1B07045085]
- Korean Health Technology R&D Project - Korean government [HI14C2434]
- Korean government
The perinuclear stacks of the Golgi apparatus maintained by dynamic microtubules are essential for cell migration. Activation of Akt (protein kinase B, PKB) negatively regulates glycogen synthase kinase 3 beta (GSK3 beta)-mediated tau phosphorylation, which enhances tau binding to microtubules and microtubule stability. In this study, experiments were performed on developmentally regulated GTP-binding protein 2 (DRG2)-stably knockdown HeLa cells to determine whether knockdown of DRG2 in HeLa cells treated with epidermal growth factor (EGF) affects microtubule dynamics, perinuclear Golgi stacking, and cell migration. Here, we show that DRG2 plays a key role in regulating microtubule stability, perinuclear Golgi stack formation, and cell migration. DRG2 knockdown prolonged the EGF receptor (EGFR) localization in endosome, enhanced Akt activity and inhibitory phosphorylation of GSK3 beta. Tau, a target of GSK3 beta, was hypo-phosphorylated in DRG2-knockdown cells and showed greater association with microtubules, resulting in microtubule stabilization. DRG2-knockdown cells showed defects in microtubule growth and microtubule organizing centers (MTOC), Golgi fragmentation, and loss of directional cell migration. These results reveal a previously unappreciated role for DRG2 in the regulation of perinuclear Golgi stacking and cell migration via its effects on GSK3 beta phosphorylation, and microtubule stability.
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