laboratoire de physique statistique
 
 
laboratoire de physique statistique

Publications

Rechercher
JOURNAL OF BIOLOGICAL CHEMISTRY 


2
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S E L E C T I O N N E R
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2016
Conserved Amphipathic Helices Mediate Lipid Droplet Targeting of Perilipins 1-3 - Rowe, Emily R. and Mimmack, Michael L. and Barbosa, Antonio D. and Haider, Afreen and Isaac, Iona and Ouberai, Myriam M. and Thiam, Abdou Rachid and Patel, Satish and Saudek, Vladimir and Siniossoglou, Symeon and Savage, David B.
JOURNAL OF BIOLOGICAL CHEMISTRY 2916664-6678 (2016)

Abstract : Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets. Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet-associated proteins, PLINs localize almost exclusively to the phospholipid monolayer surrounding the droplet. To understand how they sense and associate with the unique topology of the droplet surface, we studied the localization of human PLINs in Saccharomyces cerevisiae, demonstrating that the targeting mechanism is highly conserved and that 11-mer repeat regions are sufficient for droplet targeting. Mutations designed to disrupt folding of this region into amphipathic helices (AHs) significantly decreased lipid droplet targeting in vivo and in vitro. Finally, we demonstrated a substantial increase in the helicity of this region in the presence of detergent micelles, which was prevented by an AH-disrupting missense mutation. We conclude that highly conserved 11-mer repeat regions of PLINs target lipid droplets by folding into AHs on the droplet surface, thus enabling PLINs to regulate the interface between the hydrophobic lipid core and its surrounding hydrophilic environment.
 
2008
Functional Adhesiveness of the CX3CL1 Chemokine Requires Its Aggregation ROLE OF THE TRANSMEMBRANE DOMAIN - Hermand, Patricia and Pincet, Frederic and Carvalho, Stephanie and Ansanay, Herve and Trinquet, Eric and Daoudi, Mehdi and Combadiere, Christophe and Deterre, Philippe
JOURNAL OF BIOLOGICAL CHEMISTRY 28330225-30234 (2008)

Abstract : In its native form, the chemokine CX3CL1 is a firmly adhesive molecule promoting leukocyte adhesion and migration and hence involved, along with its unique receptor CX3CR1, in various inflammatory processes. Here we investigated the role of molecular aggregation in the CX3CL1 adhesiveness. Assays of bioluminescence resonance energy transfer (BRET) and homogeneous time-resolved fluorescence (HTRF) in transfected cell lines and in primary cells showed specific signals indicative of CX3CL1 clustering. Truncation experiments showed that the transmembrane domain played a central role in this aggregation. A chimera with mutations of the 12 central transmembrane domain residues had significantly reduced BRET signals and characteristics of a non-clustering molecule. This mutant was weakly adhesive according to flow and dual pipette adhesion assays and was less glycosylated than CX3CL1, although, as we demonstrated, loss of glycosylation did not affect the CX3CL1 adhesive potency. We postulate that cell surfaces express CX3CL1 as a constitutive oligomer and that this oligomerization is essential for its adhesive potency. Inhibition of CX3CL1 self-assembly could limit the recruitment of CX3CR1-positive cells and may be a new pathway for anti-inflammatory therapies.