https://scholars.lib.ntu.edu.tw/handle/123456789/403379
標題: | Crosstalk between AKT/GSK3β signaling and dynamin-1 regulates clathrin-mediated endocytosis | 作者: | PING-HUNG, CHEN Carlos R Reis Saipraveen Srinivasan François Aguet Marcel Mettlen Sandra L Schmid |
公開日期: | 13-八月-2015 | 卷: | 34 | 期: | 16 | 起(迄)頁: | 2132-2146 | 來源出版物: | EMBO J | 摘要: | Clathrin‐mediated endocytosis (CME) regulates signaling from the plasma membrane. Analysis of clathrin‐coated pit (CCP) dynamics led us to propose the existence of a rate‐limiting, regulatory step(s) that monitor the fidelity of early stages in CCP maturation. Here we show that nascent endocytic vesicles formed in mutant cells displaying rapid, dysregulated CME are defective in early endosomal trafficking, maturation and acidification, confirming the importance of this “checkpoint.” Dysregulated CME also alters EGF receptor signaling and leads to constitutive activation of the protein kinase Akt. Dynamin‐1, which was thought to be neuron specific, is activated by the Akt/GSK3β signaling cascade in non‐neuronal cells to trigger rapid, dysregulated CME. Acute activation of dynamin‐1 in RPE cells by inhibition of GSK3β accelerates CME, alters CCP dynamics and, unexpectedly, increases the rate of CCP initiation. CRISPR‐Cas9n‐mediated knockout and reconstitution studies establish that dynamin‐1 is activated by Akt/GSK3β signaling in H1299 non‐small lung cancer cells. These findings provide direct evidence for an isoform‐specific role for dynamin in regulating CME and reveal a feed‐forward pathway that could link signaling from cell surface receptors to the regulation of CME. |
DOI: | 10.15252/embj.201591518 |
顯示於: | 生物化學暨分子生物學科研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。