Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1.
Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1.
复制标题
脂质磷酸酶SAC1的高尔基运输和生长因子信号传导的整合。
DOI：
10.1083/jcb.200708109
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发表时间：
2008-02-25
期刊：
影响因子：
--
通讯作者：
Mayinger P
中科院分区：
文献类型：
--
作者：
Blagoveshchenskaya A;Cheong FY;Rohde HM;Glover G;Knödler A;Nicolson T;Boehmelt G;Mayinger P
当生长中的细胞扩张时，脂质和蛋白质必须被输送到它的外围。虽然这种现象已经观察了几十年，但分泌途径如何响应生长信号仍不清楚。我们证明，控制高尔基磷脂酰肌醇-4-磷酸(PI(4)P)是生长相关分泌所必需的。在静止的细胞中，磷酸肌醇磷酸酶SAC1聚集在高尔基体上，通过耗尽高尔基体PI(4)P来下调顺行转运。高尔基体定位需要SAC1的寡聚和外壳蛋白(COP)II复合体的募集。当静止细胞被有丝分裂原刺激时，SAC1迅速穿梭回内质网(ER)，从而释放对高尔基体分泌的刹车。P38丝裂原活化激酶(MAPK)通路在丝裂原刺激后诱导SAC1寡聚体的解离，从而触发COP-I介导的SAC1向内质网的恢复。抑制p38MAPK可消除生长因子诱导的SAC1高尔基体到内质网的穿梭，并减缓其分泌。这些结果表明，p38MAPK和SAC1在向分泌机制传递生长信号方面发挥了直接作用。
When a growing cell expands, lipids and proteins must be delivered to its periphery. Although this phenomenon has been observed for decades, it remains unknown how the secretory pathway responds to growth signaling. We demonstrate that control of Golgi phosphatidylinositol-4-phosphate (PI(4)P) is required for growth-dependent secretion. The phosphoinositide phosphatase SAC1 accumulates at the Golgi in quiescent cells and down-regulates anterograde trafficking by depleting Golgi PI(4)P. Golgi localization requires oligomerization of SAC1 and recruitment of the coat protein (COP) II complex. When quiescent cells are stimulated by mitogens, SAC1 rapidly shuttles back to the endoplasmic reticulum (ER), thus releasing the brake on Golgi secretion. The p38 mitogen-activated kinase (MAPK) pathway induces dissociation of SAC1 oligomers after mitogen stimulation, which triggers COP-I–mediated retrieval of SAC1 to the ER. Inhibition of p38 MAPK abolishes growth factor–induced Golgi-to-ER shuttling of SAC1 and slows secretion. These results suggest direct roles for p38 MAPK and SAC1 in transmitting growth signals to the secretory machinery.