How Golgi lipids drive growth factor signaling at the plasma membrane

脂质是包围不同细胞器的细胞膜的基本成分，通过形成质膜，包围整个细胞。质膜的精确脂质组成决定了其流动性，是膜微域形成的基础。这些微结构域富含鞘磷脂和胆固醇，它们的合成主要发生在高尔基复合体中。最近的证据表明，脂质转移蛋白CERT通过将神经酰胺作为鞘磷脂合成的前体从内质网转运到高尔基膜，在脂质稳态中起关键作用。在这个项目中，我们的目的是研究cert依赖的高尔基复合体脂质合成与质膜信号事件之间的关系。我们希望解决质膜的脂质组成如何影响生长因子受体的信号特性。在这里，我们将重点关注ErbB受体酪氨酸激酶家族在自磷酸化、横向移动、内化和细胞内信号通路激活方面的作用。我们进一步分析了生长因子诱导的细胞极化和迁移对CERT表达的依赖性。这些研究有望有助于全面了解局部脂质合成和膜特性对跨膜受体活性及其细胞反应的影响。

Lipids are essential components of cellular membranes that surround the different organelles and, by forming a plasma membrane, the entire cell. The precise lipid composition of the plasma membrane determines its fluidity and is the basis for the formation of membrane microdomains. These microdomains are enriched in sphingomyelin and cholesterol whose synthesis primarily occurs at the Golgi complex. Recent evidence suggests that the lipid transfer protein CERT plays a critical role in lipid homeostasis by shuttling ceramide as a precursor for sphingomyelin synthesis from the ER to Golgi membranes. In this project we aim to investigate the relationship between CERT-dependent lipid synthesis at the Golgi complex and signaling events at the plasma membrane. We wish to address how lipid composition of the plasma membrane impacts on the signaling properties of growth factor receptors. Here we will focus on the ErbB family of receptor tyrosine kinases with regard to autophosphorylation, lateral mobility, internalization and the activation of intracellular signaling pathways. We further aim to analyze growth factor-induced cell polarization and migration in dependence of CERT expression. These studies are expected to contribute to a global understanding of the influence of local lipid synthesis and membrane properties on the activity of transmembrane receptors and their cellular responses.