CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain
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...
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2014-11-01
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doaj-043fce7c655a401abb7b6253bbac284c2021-06-02T17:52:27ZengThe Company of BiologistsBiology Open2046-63902014-11-013121173118210.1242/bio.2014984520149845CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domainMariano A. Ostuni0Julie Guellec1Patricia Hermand2Pauline Durand3Christophe Combadière4Frédéric Pincet5Philippe Deterre6 INSERM, U 1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013, Paris, France INSERM, U 1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013, Paris, France INSERM, U 1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMR 94550 ENS Laboratoire de Physique Statistique, F-75005, Paris, France INSERM, U 1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMR 94550 ENS Laboratoire de Physique Statistique, F-75005, Paris, France INSERM, U 1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013, Paris, France 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.http://bio.biologists.org/content/3/12/1173ChemokineAdhesionFRAPGlycosylationGPCR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mariano A. Ostuni Julie Guellec Patricia Hermand Pauline Durand Christophe Combadière Frédéric Pincet Philippe Deterre |
spellingShingle |
Mariano A. Ostuni Julie Guellec Patricia Hermand Pauline Durand Christophe Combadière Frédéric Pincet Philippe Deterre CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain Biology Open Chemokine Adhesion FRAP Glycosylation GPCR |
author_facet |
Mariano A. Ostuni Julie Guellec Patricia Hermand Pauline Durand Christophe Combadière Frédéric Pincet Philippe Deterre |
author_sort |
Mariano A. Ostuni |
title |
CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
title_short |
CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
title_full |
CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
title_fullStr |
CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
title_full_unstemmed |
CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
title_sort |
cx3cl1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2014-11-01 |
description |
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. |
topic |
Chemokine Adhesion FRAP Glycosylation GPCR |
url |
http://bio.biologists.org/content/3/12/1173 |
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