Department of Biochemistry and Biomedical Sciences, McMaster University, Health Sciences Centre, Hamilton, Ontario, L8S 4K1, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Health Sciences Centre, Hamilton, Ontario, L8S 4K1, Canada.
Chem Phys Lipids. 2019 Jul;221:24-29. doi: 10.1016/j.chemphyslip.2019.03.002. Epub 2019 Mar 6.
The extensive number of metabolic processes regulated by phosphatidylinositol (PI) phospholipids highlights their physiological importance. The major metabolic pathway for their biosynthesis in cells is the PI-cycle. Contrary to most metabolic cycles, reactions of the PI-cycle occur in two different locations; those are, the plasma membrane (PM) and endoplasmic reticulum (ER). Lipid movement between the two organelles is, therefore, a requirement of the cyclical process. Moreover, in mammals the PI-cycle yield PI molecular species enriched in specific acyl chains, namely 1-stearoyl-2-arachidonoyl acyl chains. Hence, to ensure cycle efficiency and specificity it should take place in specialized regions of PM and ER rather than being randomly distributed among those membranes. Along these lines, ER-PM contact sites have emerged as the location where a number of proteins related to the PI-cycle have been reported to localize. Of importance to this review is the presence of the epsilon isoform of diacylglycerol kinase (DGKε) at ER-PM contact sites. In the PI-cycle DGKε is in part responsible for the acyl chain enrichment of the PI molecular species. However, it has recently been shown that the enzyme can only engage in the PI-cycle upon membrane morphological changes. In this review we will discuss the PI-cycle at ER-PM contact sites and how the generation of membrane negative Gaussian curvature nearby those regions could regulate the cycle. We will focus our discussion on the hypothesis that actin polymerization provides the mechanical force needed to change membrane shape nearby ER-PM contact sites, which will transiently trigger DGKε and, therefore, link enzymatic catalysis and lipid transfer in the PI-cycle.
磷脂酰肌醇（PI）磷脂调节的大量代谢过程突出了其生理重要性。细胞中其生物合成的主要代谢途径是 PI 循环。与大多数代谢循环相反，PI 循环的反应发生在两个不同的位置；即，质膜（PM）和内质网（ER）。因此，两细胞器之间的脂质运动是循环过程的要求。此外，在哺乳动物中，PI 循环产生富含特定酰基链的 PI 分子种类，即 1-硬脂酰-2-花生四烯酰酰基链。因此，为了确保循环效率和特异性，它应该发生在 PM 和 ER 的专门区域，而不是随机分布在这些膜之间。沿着这些思路，ER-PM 接触位点已经出现，许多与 PI 循环相关的蛋白质已被报道定位于该位置。对本篇综述重要的是，二酰基甘油激酶（DGKε）的 ε 同工型存在于 ER-PM 接触位点。在 PI 循环中，DGKε 部分负责 PI 分子种类的酰基链富集。然而，最近表明，只有在膜形态发生变化时，该酶才能参与 PI 循环。在这篇综述中，我们将讨论 ER-PM 接触位点处的 PI 循环，以及附近区域的膜负高斯曲率的产生如何调节该循环。我们将重点讨论以下假设：肌动蛋白聚合提供了改变 ER-PM 接触位点附近膜形状所需的机械力，这将瞬时触发 DGKε，从而将酶促催化和 PI 循环中的脂质转移联系起来。
