NDLI: Functional adhesiveness of the CX3CL1 chemokine requires its aggregation. Role of the transmembrane domain.

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Functional adhesiveness of the CX3CL1 chemokine requires its aggregation. Role of the transmembrane domain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Daoudi, Mehdi Pincet, Frédéric Trinquet, Eric Deterre, Philippe Combadière, Christophe Ansanay, Hervé Hermand, Patricia Carvalho, Stéphanie
Description	Author Affiliation: Hermand P ( Laboratoire d'Immunologie Cellulaire, INSERM UMR-S 543, Université Pierre et Marie Curie-Paris 06, 91 boulevard de l'Hôpital, 75013 Paris, France.)
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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	44
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-10-31
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chemokine CX3CL1 Metabolism Mutation Amino Acid Sequence Anti-Inflammatory Agents Pharmacology Cell Adhesion Cell Line Gene Deletion Glycosylation Inflammation Models, Biological Molecular Sequence Data Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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