Golgi-associated GSK3β regulates the sorting process of post-Golgi membrane trafficking
Golgi-associated GSK3β regulates the sorting process of post-Golgi membrane trafficking
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DOI：
10.1242/jcs.063941
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Murata, Masayuki
中科院分区：
文献类型：
--
作者：
Adachi, Atsuhiro;Kano, Fumi;Murata, Masayuki
糖原合酶激酶 beta (GSK3 beta) 磷酸化哺乳动物细胞中的许多底物，并在许多生理过程中发挥作用。我们观察到，siRNA 敲低 GSK3 beta 扰乱了 HeLa 细胞中的高尔基体形态，以及阳离子独立的甘露糖 6-磷酸受体 (CI-M6PR) 从跨高尔基体网络 (TGN) 到前溶酶体区室 (PLC) 的顺行转运，将其转向胞吐途径。此外，我们证明 GSK3 β 的一部分通过高尔基体外周蛋白 p230 定位于 TGN，并且该定位调节 CLASP2 磷酸化。我们的结果还表明，GSK3 beta 敲低导致 CLASP2 在细胞外周的微管正端积累。我们的研究结果支持这样的假设：TGN 处的 GSK3 beta 充当向导，激活胞吐转运，并通过调节 CLASP 对微管的亲和力将 CI-M6PR 从运输到 PLC 重定向到胞吐途径。
Glycogen synthase kinase beta (GSK3 beta) phosphorylates many substrates in mammalian cells, and functions in many physiological processes. We observed that GSK3 beta knockdown by siRNA perturbed both Golgi morphology in HeLa cells and the anterograde transport of cation-independent mannose 6-phosphate receptor (CI-M6PR) from the trans-Golgi network (TGN) to prelysosomal compartments (PLC), diverting it to the exocytic pathway. Moreover, we demonstrate that a portion of GSK3 beta was localized to the TGN through the Golgi peripheral protein p230 and that this localization regulated CLASP2 phosphorylation. Our results also show that GSK3 beta knockdown resulted in accumulation of CLASP2 at microtubule plus ends at the cell periphery. Our findings support the hypothesis that GSK3 beta at the TGN acts as a guide, activates exocytic transport, and redirects CI-M6PR from transport to the PLC into the exocytic pathway by regulating the affinity of CLASPs for microtubules.