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Roles of Palmitoylation networks in ER architecture and functions

Objective

The endoplasmic reticulum (ER) is the largest intracellular organelle of mammalian cells. It fulfills major functions such as folding and quality control of membrane proteins, lipid biosynthesis, calcium storage, and modulation of apoptosis. 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 Our unpublished observations show that many ER membrane proteins, involved in key functions or in organelle shaping, are lipid modified, by the same palmitoyltransferases, and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 hypothesize that palmitoyltransferases act as regulators of the mammalian ER, controlling the function 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 and modeling approaches. We will determine the ER palmitome and investigate the impact of acylation on the function of individual proteins, on ER architecture and on the ER lipidome. We will analyze the interplay between and ubiquitination in controlling ER functions. Since we found that the DHHC6 palmitoytransferase is essential in mice and palmitoylates key ER proteins, we will study this enzyme in depth in terms of structure, function, target specific and regulation. Finally, we will combine the information emanating from these studies into a mathematical model of the ER palmitoylation network.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

ERC-2013-ADG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Address
Batiment Ce 3316 Station 1
1015 Lausanne
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 443 949
Principal investigator
Francoise Gisou Van Der Goot (Prof.)
Administrative Contact
Caroline Vandevyver (Dr.)

Beneficiaries (1)

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland
EU contribution
€ 2 443 949
Address
Batiment Ce 3316 Station 1
1015 Lausanne
Activity type
Higher or Secondary Education Establishments
Principal investigator
Francoise Gisou Van Der Goot (Prof.)
Administrative Contact
Caroline Vandevyver (Dr.)