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Membrane sensors in the Arf orbit

Objective

Cellular organelles are continuously remodelled by numerous cytosolic proteins that associate transiently with their lipid membrane. Some distort the bilayer, others change its composition, extract lipids or bridge membranes at distance. Previous works from my laboratory have underlined the importance of membrane sensors, i.e. elements within proteins that help to organize membrane-remodelling events by sensing the physical and chemical state of the underlying membrane. A membrane sensor is not necessarily of well-folded domain that interacts with a specific lipid polar head: some intrinsically unfolded motifs harboring deceptively simple sequences can display remarkable membrane adhesive properties. Among these are some amphipathic helices: the ALPS motif with a polar face made mostly by small uncharged polar residues, the Spo20 helix with several histidines in its polar face and, like a mirror image of the ALPS motif, the alpha-synuclein helix with very small hydrophobic residues. Using biochemistry and molecular dynamics, we will compare the membrane binding properties of these sequences (effect of curvature, charge, lipid unsaturation); using bioinformatics we will look for new motifs, using cell biology we will assess the adaptation of these motifs to the physical and chemical features of organelle membranes. Concurrently, we will use reconstitution approaches on artificial membranes to dissect how membrane sensors contribute to the organization of vesicle tethering by golgins and sterol transport by ORP proteins. We surmise that the combination of a molecular ¿switch¿, a small G protein of the Arf family, and of membrane sensors permit to organize these complex reactions in time and in space.

Call for proposal

ERC-2010-AdG_20100317
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Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Address
Rue Michel Ange 3
75794 Paris
France
Activity type
Other
EU contribution
€ 1 917 925,40
Principal investigator
Bruno Antonny (Dr.)
Administrative Contact
Béatrice Saint-Cricq (Ms.)

Beneficiaries (2)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 1 917 925,40
Address
Rue Michel Ange 3
75794 Paris
Activity type
Other
Principal investigator
Bruno Antonny (Dr.)
Administrative Contact
Béatrice Saint-Cricq (Ms.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 79 395,60
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Véronique Legros (Ms.)