Official websites use. Share sensitive information only on official, secure websites. Leclerc, Lille Cedex, France. Fax: ; E-mail: deterre ccr. 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. 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. Migration of circulating leukocytes to injury sites is the first step of the inflammation process, which involves a sequence of coordinated interactions between leukocytes and endothelial cells 1. Central to this physiological and pathological event are chemokines, a family of low molecular weight soluble proteins, that function to attract leukocytes bearing the appropriate receptors 2.
Chemokines trigger activation of leukocytes and their firm adhesion to inflamed endothelium, mainly through the mediation of integrins and their cognate ligands 3. In addition to their chemokine domain CD , 4 they are composed of a long mucin-like stalk, a transmembrane domain, and a cytoplasmic tail 4 , 5 Fig.
