CX3CL1, a Chemokine Finely Tuned to Adhesion: Critical Roles of the Stalk Glycosylation and the Membrane Domain

Overview

Journal Biol Open

Specialty Biology

Date 2014 Nov 15

PMID 25395671

Citations 25

Authors

Mariano A Ostuni

Julie Guellec

Patricia Hermand

Pauline Durand

Christophe Combadiere

Frederic Pincet

Philippe Deterre

Affiliations

Soon will be listed here.

Abstract

The multi-domain CX3CL1 transmembrane chemokine triggers leukocyte adherence without rolling and migration by presenting its chemokine domain (CD) to its receptor CX3CR1. Through the combination of functional adhesion assays with structural analysis using FRAP, we investigated the functional role of the other domains of CX3CL1, i.e., its mucin stalk, transmembrane domain, and cytosolic domain. Our results indicate that the CX3CL1 molecular structure is finely adapted to capture CX3CR1 in circulating cells and that each domain has a specific purpose: the mucin stalk is stiffened by its high glycosylation to present the CD away from the membrane, the transmembrane domain generates the permanent aggregation of an adequate amount of monomers to guarantee adhesion and prevent rolling, and the cytosolic domain ensures adhesive robustness by interacting with the cytoskeleton. We propose a model in which quasi-immobile CX3CL1 bundles are organized to quickly generate adhesive patches with sufficiently high strength to capture CX3CR1+ leukocytes but with sufficiently low strength to allow their patrolling behavior.

Citing Articles

Aging Microglia and Their Impact in the Nervous System.

von Bernhardi R, Eugenin J Adv Neurobiol. 2024; 37:379-395.

PMID: 39207703 DOI: 10.1007/978-3-031-55529-9_21.

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis.

Szukiewicz D Int J Mol Sci. 2024; 25(9).

PMID: 38731899 PMC: 11083509. DOI: 10.3390/ijms25094679.

Alterations in CX3CL1 Levels and Its Role in Viral Pathogenesis.

Zhang C, Zhang Y, Zhuang R, Yang K, Chen L, Jin B Int J Mol Sci. 2024; 25(8).

PMID: 38674036 PMC: 11050295. DOI: 10.3390/ijms25084451.

Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases.

Eugenin J, Eugenin-von Bernhardi L, von Bernhardi R Front Mol Neurosci. 2023; 16:1249320.

PMID: 37818457 PMC: 10561274. DOI: 10.3389/fnmol.2023.1249320.

CX3CL1 Derived from Bone Marrow Mesenchymal Stem Cells Inhibits A -Induced SH-SY5Y Cell Pathological Damage through TXNIP/NLRP3 Signaling Pathway.

Guo C, Li Q, Xiao J, Zhou X, Tian M, Xie L Comput Math Methods Med. 2022; 2022:1949344.

PMID: 36118839 PMC: 9477634. DOI: 10.1155/2022/1949344.

References

Kucik D, Dustin M, Miller J, Brown E . Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes. J Clin Invest. 1996; 97(9):2139-44. PMC: 507289. DOI: 10.1172/JCI118651. View

Kusumi A, Suzuki K, Koyasako K . Mobility and cytoskeletal interactions of cell adhesion receptors. Curr Opin Cell Biol. 1999; 11(5):582-90. DOI: 10.1016/s0955-0674(99)00020-4. View

Lee F, Haskell C, Charo I, Boettiger D . Receptor-ligand binding in the cell-substrate contact zone: a quantitative analysis using CX3CR1 and CXCR1 chemokine receptors. Biochemistry. 2004; 43(22):7179-86. DOI: 10.1021/bi0362121. View

Hundhausen C, Misztela D, Berkhout T, Broadway N, Saftig P, Reiss K . The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 2003; 102(4):1186-95. DOI: 10.1182/blood-2002-12-3775. View

Cipriani R, Villa P, Chece G, Lauro C, Paladini A, Micotti E . CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. J Neurosci. 2011; 31(45):16327-35. PMC: 6633249. DOI: 10.1523/JNEUROSCI.3611-11.2011. View

Combadiere B, Combadiere C, Deterre P . [Chemokines: a sophisticated cell-guidance network]. Med Sci (Paris). 2007; 23(2):173-9. DOI: 10.1051/medsci/2007232173. View

Kerfoot S, Lord S, Bell R, Gill V, Robbins S, Kubes P . Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment. Eur J Immunol. 2003; 33(3):729-39. DOI: 10.1002/eji.200323502. View

Wier M, Edidin M . Constraint of the translational diffusion of a membrane glycoprotein by its external domains. Science. 1988; 242(4877):412-4. DOI: 10.1126/science.3175663. View

Krieger M, Brown M, Goldstein J . Isolation of Chinese hamster cell mutants defective in the receptor-mediated endocytosis of low density lipoprotein. J Mol Biol. 1981; 150(2):167-84. DOI: 10.1016/0022-2836(81)90447-2. View

10.

Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M . Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 1997; 91(4):521-30. DOI: 10.1016/s0092-8674(00)80438-9. View

11.

Gambin Y, Lopez-Esparza R, Reffay M, Sierecki E, Gov N, Genest M . Lateral mobility of proteins in liquid membranes revisited. Proc Natl Acad Sci U S A. 2006; 103(7):2098-102. PMC: 1413751. DOI: 10.1073/pnas.0511026103. View

12.

Hermand P, Pincet F, Carvalho S, Ansanay H, Trinquet E, Daoudi M . Functional adhesiveness of the CX3CL1 chemokine requires its aggregation. Role of the transmembrane domain. J Biol Chem. 2008; 283(44):30225-34. PMC: 2662081. DOI: 10.1074/jbc.M802638200. View

13.

Soumpasis D . Theoretical analysis of fluorescence photobleaching recovery experiments. Biophys J. 1983; 41(1):95-7. PMC: 1329018. DOI: 10.1016/S0006-3495(83)84410-5. View

14.

Wakatsuki T, Schwab B, Thompson N, Elson E . Effects of cytochalasin D and latrunculin B on mechanical properties of cells. J Cell Sci. 2001; 114(Pt 5):1025-36. DOI: 10.1242/jcs.114.5.1025. View

15.

Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S . Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007; 317(5838):666-70. DOI: 10.1126/science.1142883. View

16.

Simon S, Sarantos M, Green C, Schaff U . Leucocyte recruitment under fluid shear: mechanical and molecular regulation within the inflammatory synapse. Clin Exp Pharmacol Physiol. 2008; 36(2):217-24. DOI: 10.1111/j.1440-1681.2008.05083.x. View

17.

He H, Marguet D . T-cell antigen receptor triggering and lipid rafts: a matter of space and time scales. Talking Point on the involvement of lipid rafts in T-cell activation. EMBO Rep. 2008; 9(6):525-30. PMC: 2427382. DOI: 10.1038/embor.2008.78. View

18.

Evans E . Probing the relation between force--lifetime--and chemistry in single molecular bonds. Annu Rev Biophys Biomol Struct. 2001; 30:105-28. DOI: 10.1146/annurev.biophys.30.1.105. View

19.

Charo I, Ransohoff R . The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006; 354(6):610-21. DOI: 10.1056/NEJMra052723. View

20.

Braeckmans K, Peeters L, Sanders N, De Smedt S, Demeester J . Three-dimensional fluorescence recovery after photobleaching with the confocal scanning laser microscope. Biophys J. 2003; 85(4):2240-52. PMC: 1303450. DOI: 10.1016/S0006-3495(03)74649-9. View