Phosphoinositide kinase signaling controls ER-PM cross-talk.
Phosphoinositide kinase signaling controls ER-PM cross-talk.
复制标题
DOI：
10.1091/mbc.e16-01-0002
复制
发表时间：
2016-04-01
影响因子：
3.3
通讯作者：
Stefan CJ
中科院分区：
文献类型：
--
作者：
Omnus DJ;Manford AG;Bader JM;Emr SD;Stefan CJ
磷酸肌醇激酶信号传导控制保守的PDK-TORC 2-Akt信号传导级联，作为稳态网络的一部分，其允许ER调节质膜（PM）应激时的基本应答，包括Ca 2+调节的脂质生物合成。ER-PM结的损失损害了这种保护性反应，导致热应力时PM完整性缺陷。膜脂质动力学必须被精确地调节以实现正常的细胞功能，并且脂质稳态的破坏与若干疾病的进展有关。然而，鲜为人知的是，用于检测膜组成的感觉机制，以及如何调节脂质代谢反应膜应力。我们发现，磷酸肌醇（PI）激酶信号控制一个保守的PDK-TORC 2-Akt信号级联作为一个稳态网络的一部分，允许内质网（ER）调节必要的反应，包括Ca 2+调节的脂质生物合成，质膜（PM）的压力。此外，ER-PM结的损失损害了这种保护性反应，导致热应力时PM完整性缺陷。因此，PI激酶介导的ER-PM串扰包括在膜应激条件下确保细胞完整性的调节系统。
Phosphoinositide kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the ER to modulate essential responses, including Ca2+-regulated lipid biogenesis, upon plasma membrane (PM) stress. Loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in lipid homeostasis are linked to the progression of several diseases. However, little is known about the sensory mechanisms for detecting membrane composition and how lipid metabolism is regulated in response to membrane stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the endoplasmic reticulum (ER) to modulate essential responses, including Ca2+-regulated lipid biogenesis, upon plasma membrane (PM) stress. Furthermore, loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Thus PI kinase–mediated ER-PM cross-talk comprises a regulatory system that ensures cellular integrity under membrane stress conditions.