How Golgi lipids drive growth factor signaling at the plasma membrane

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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.