Gisou Van der Goot, Palmitoylation networks in the ER
© 2013 EPFL
Françoise Gisou Van der Goot, head of Laboratory of Cell and Membrane Biology, has been awarded an ADVANCED GRANT 2013 from the European Research Council (ERC). The excellence of the research performed at EPFL has once again been recognized at an international level.
Roles of Palmitoylation networks in the ER architecture and functions
The endoplasmic reticulum (ER) is the largest intracellular organelle of mammalian cells. It fulfills major functions such as folding and quality control of membrane and secreted proteins, lipid biosynthesis and calcium storage. This diversity of functions is accompanied by a complex 3D architecture, the maintenance of which is essential, since alterations lead to disease. How this architecture is generated, how proteins localize to specific subdomains and how structure and functions are coordinated is poorly understood. Our unpublished observations show that many ER membrane proteins, involved in key functions or in organelle shaping, are lipid modified, by the same palmitoyltransferases, and in a switch-like manner. We therefore hypothesize that palmitoyltransferases act as master regulators of the mammalian ER, controlling the function/behavior of a network of key proteins through reversible acylation, analogous to the control of signaling networks by phosphorylation. To establish the role of palmitoylation in coordinating ER structure/function, we propose a program integrating biochemical, functional, modeling and genomic approaches. We will determine the ER palmitome and investigate the impact of acylation on the function of individual proteins. We will investigate how palmitoylation of specific proteins and changes in ER architecture control the lipidome of ER domains. We will analyze the competition between protein palmitoylation and ubiquitination in controlling protein function. Finally, we will combine the information emanating from these studies into a mathematical model of the ER palmitoylation network. Our demonstrated ability for multidisciplinary research, our expertise in membrane biology, protein folding, trafficking and palmitoylation and the establishment of appropriate collaborations put us in a unique position to address these important open questions and introduce a novel perspective in the studies of ER function.
Host institution: EPFL
Project acronym: PalmERa
Domain: Life Sciences