CX3CL1 homo-oligomerization drives cell-to-cell adherence
Mariano A. Ostuni
(1)
,
Patricia Hermand
(1)
,
Emeline Saindoy
,
Noëlline Guillou
(2)
,
Julie Guellec
(3)
,
Audrey Coens
(4, 5)
,
Claude Hattab
(6)
,
Elodie Desuzinges-Mandon
(7)
,
Anass Jawhari
(8)
,
Soria Iatmanen-Harbi
(9)
,
Olivier Lequin
(10)
,
Patrick Fuchs
(11)
,
Jean-Jacques Lacapère
(12)
,
Christophe Combadière
(1)
,
Frédéric Pincet
(13)
,
Philippe Deterre
(1)
1
CIMI -
Centre d'Immunologie et de Maladies Infectieuses
2 IEM - Immunologie et Embryologie Moléculaires
3 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
4 I2BC - Institut de Biologie Intégrative de la Cellule
5 CIMI - Centre d'Immunologie et des Maladies Infectieuses
6 DSIMB - Dynamique des Structures et Interactions des Macromolécules Biologiques
7 CNRS - Centre National de la Recherche Scientifique
8 CALIXAR
9 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
10 UPMC - Université Pierre et Marie Curie - Paris 6
11 EA3305 - Laboratoire de Spectroscopies et Structures Biomoléculaires (LSSBM)
12 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
13 YSM - Yale School of Medicine [New Haven, Connecticut]
2 IEM - Immunologie et Embryologie Moléculaires
3 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
4 I2BC - Institut de Biologie Intégrative de la Cellule
5 CIMI - Centre d'Immunologie et des Maladies Infectieuses
6 DSIMB - Dynamique des Structures et Interactions des Macromolécules Biologiques
7 CNRS - Centre National de la Recherche Scientifique
8 CALIXAR
9 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
10 UPMC - Université Pierre et Marie Curie - Paris 6
11 EA3305 - Laboratoire de Spectroscopies et Structures Biomoléculaires (LSSBM)
12 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
13 YSM - Yale School of Medicine [New Haven, Connecticut]
Mariano A. Ostuni
- Fonction : Auteur
- PersonId : 16543
- IdHAL : mariano-ostuni
- ORCID : 0000-0001-6769-3786
- IdRef : 177420847
Emeline Saindoy
- Fonction : Auteur
Olivier Lequin
- Fonction : Auteur
- PersonId : 760055
- ORCID : 0000-0001-5307-3068
- IdRef : 127152601
Patrick Fuchs
- Fonction : Auteur
- PersonId : 843129
Christophe Combadière
- Fonction : Auteur
- PersonId : 735799
- IdHAL : christophe-combadiere
- ORCID : 0000-0002-1755-4531
- IdRef : 088646041
Frédéric Pincet
- Fonction : Auteur
- PersonId : 738933
- IdHAL : frederic-pincet
- ORCID : 0000-0002-4243-2157
- IdRef : 110329945
Résumé
During inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1, which behaves as a molecular cluster. How this cluster assembles and whether this association has a functional role remain unknown. The analysis of CX3CL1 clusters using native electrophoresis and single molecule fluorescence kinetics shows that CX3CL1 is a homo-oligomer of 3 to 7 monomers. Fluorescence recovery after photobleaching assays reveal that the CX3CL1-transmembrane domain peptide self-associates in both cellular and acellular lipid environments, while its random counterpart (i.e. peptide with the same residues in a different order) does not. This strongly indicates that CX3CL1 oligomerization is driven by its intrinsic properties. According to the molecular modeling, CX3CL1 does not associate in compact bundles but rather with monomers linearly assembled side by side. Finally, the CX3CL1 transmembrane peptide inhibits both the CX3CL1 oligomerization and the adhesive function, while its random counterpart does not. This demonstrates that CX3CL1 oligomerization is mandatory for its adhesive potency. Our results provide a new direction to control CX3CL1-dependent cellular adherence in key immune processes. The migration of blood leukocytes to damaged tissues is the first step of the inflammation process and involves a sequence of coordinated interactions between leukocytes and endothelial cells 1-3. The chemotactic cytokines called chemokines that primarily attract leukocytes, are central to the physiological and pathological inflamma-tory processes 4-6. Chemokines trigger leukocyte activation and their firm adhesion to the inflamed endothelium, mainly through integrins 7-9. Two members of the chemokine family are exceptions: CXCL16 and CX3CL1. In addition to their chemokine domain (CD), these two chemokines possess three domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail 10,11. When interacting with their cognate receptors (CXCR6 and CX3CR1, respectively), these chemokines induce cell-cell adhesion 12. CXCL16 and CX3CL1 can also be cleaved by metalloproteinases, such as ADAM10 and ADAM17 13-15 , to produce a soluble form with chemotactic functions. The CX3CL1 chemokine, with its unique CX3CR1 receptor 16 , is involved in adherence to the endothelium of the inflammatory monocyte population (CD14 hi CD16-CX3CR1 + CCR2 + in humans, Ly6C hi CX3CR1 + CCR2 + in mice) 12,17-20 likely through interaction with platelets 21,22. This chemokine is also involved in the recruitment of NK lymphocytes 23,24 and in lymphocyte survival as in allergic diseases 25 , as well as in monocytic 26,27 and neuronal survival 28-31. An additional function of the CX3CR1-CX3CL1 pair is the regulation of the patrolling behavior and the margination of monocytes in blood vessels 32,33 or their adherence to the bone marrow 34. The CX3CL1 chemokine is also involved in cytoadhesion of red blood cells infected with the malaria parasite Plasmodium
Domaines
ImmunologieFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Résumé |
en
During inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1, which behaves as a molecular cluster. How this cluster assembles and whether this association has a functional role remain unknown. The analysis of CX3CL1 clusters using native electrophoresis and single molecule fluorescence kinetics shows that CX3CL1 is a homo-oligomer of 3 to 7 monomers. Fluorescence recovery after photobleaching assays reveal that the CX3CL1-transmembrane domain peptide self-associates in both cellular and acellular lipid environments, while its random counterpart (i.e. peptide with the same residues in a different order) does not. This strongly indicates that CX3CL1 oligomerization is driven by its intrinsic properties. According to the molecular modeling, CX3CL1 does not associate in compact bundles but rather with monomers linearly assembled side by side. Finally, the CX3CL1 transmembrane peptide inhibits both the CX3CL1 oligomerization and the adhesive function, while its random counterpart does not. This demonstrates that CX3CL1 oligomerization is mandatory for its adhesive potency. Our results provide a new direction to control CX3CL1-dependent cellular adherence in key immune processes. The migration of blood leukocytes to damaged tissues is the first step of the inflammation process and involves a sequence of coordinated interactions between leukocytes and endothelial cells 1-3. The chemotactic cytokines called chemokines that primarily attract leukocytes, are central to the physiological and pathological inflamma-tory processes 4-6. Chemokines trigger leukocyte activation and their firm adhesion to the inflamed endothelium, mainly through integrins 7-9. Two members of the chemokine family are exceptions: CXCL16 and CX3CL1. In addition to their chemokine domain (CD), these two chemokines possess three domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail 10,11. When interacting with their cognate receptors (CXCR6 and CX3CR1, respectively), these chemokines induce cell-cell adhesion 12. CXCL16 and CX3CL1 can also be cleaved by metalloproteinases, such as ADAM10 and ADAM17 13-15 , to produce a soluble form with chemotactic functions. The CX3CL1 chemokine, with its unique CX3CR1 receptor 16 , is involved in adherence to the endothelium of the inflammatory monocyte population (CD14 hi CD16-CX3CR1 + CCR2 + in humans, Ly6C hi CX3CR1 + CCR2 + in mice) 12,17-20 likely through interaction with platelets 21,22. This chemokine is also involved in the recruitment of NK lymphocytes 23,24 and in lymphocyte survival as in allergic diseases 25 , as well as in monocytic 26,27 and neuronal survival 28-31. An additional function of the CX3CR1-CX3CL1 pair is the regulation of the patrolling behavior and the margination of monocytes in blood vessels 32,33 or their adherence to the bone marrow 34. The CX3CL1 chemokine is also involved in cytoadhesion of red blood cells infected with the malaria parasite Plasmodium
|
Titre |
en
CX3CL1 homo-oligomerization drives cell-to-cell adherence
|
Auteur(s) |
Mariano A. Ostuni
1
, Patricia Hermand
1
, Emeline Saindoy
, Noëlline Guillou
2
, Julie Guellec
3
, Audrey Coens
4, 5
, Claude Hattab
6
, Elodie Desuzinges-Mandon
7
, Anass Jawhari
8
, Soria Iatmanen-Harbi
9
, Olivier Lequin
10
, Patrick Fuchs
11
, Jean-Jacques Lacapère
12
, Christophe Combadière
1
, Frédéric Pincet
13
, Philippe Deterre
1
1
CIMI -
Centre d'Immunologie et de Maladies Infectieuses
( 246601 )
- 91 Boulevard de l'hôpital 75013 Paris
- France
2
IEM -
Immunologie et Embryologie Moléculaires
( 20032 )
- Institut de Transgénose - 3B rue de la Ferollerie - 45071 ORLEANS CEDEX 2
- France
3
GGB -
Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
( 182183 )
- UFR Médecine
22 avenue Camille Desmoulins
29238 BREST Cedex 3
- France
4
I2BC -
Institut de Biologie Intégrative de la Cellule
( 414518 )
- Bâtiment 21, 1 avenue de la Terrasse, 91198 Gif/Yvette cedex
- France
5
CIMI -
Centre d'Immunologie et des Maladies Infectieuses
( 542033 )
- 91 Boulevard de l'hôpital 75013 Paris
- France
6
DSIMB -
Dynamique des Structures et Interactions des Macromolécules Biologiques
( 266751 )
- 6 rue Alexandre Cabanel, 75739 Paris cedex 15
- France
7
CNRS -
Centre National de la Recherche Scientifique
( 441569 )
- France
8
CALIXAR
( 540951 )
- 60 Ave Rockefeller, F-69008 Lyon
- France
9
CRI (UMR_S_1149 / ERL_8252 / U1149) -
Centre de recherche sur l'Inflammation
( 246564 )
- Faculté de Médecine site Bichat - 16, Rue Henri Huchard - BP 416/4ème étage - 75870 Paris Cedex 18
- France
10
UPMC -
Université Pierre et Marie Curie - Paris 6
( 93591 )
- 4 place Jussieu - 75005 Paris
- France
11
EA3305 -
Laboratoire de Spectroscopies et Structures Biomoléculaires (LSSBM)
( 12727 )
- Université de Reims Champagne Ardenne - UFR Sciences - Moulin de la Housse - BP 1039 - 51687 Reims cedex 2 - France
- France
12
CRB3 -
Centre de recherche biomédicale Bichat-Beaujon
( 3041 )
- Faculte de Medecine Xavier Bichat 16, Rue Henri Huchard 75870 PARIS CEDEX 18
- France
13
YSM -
Yale School of Medicine [New Haven, Connecticut]
( 51214 )
- Yale University School of Medicine - 333 Cedar Street - New Haven, CT 06510
- États-Unis
|
Page/Identifiant |
9069
|
Comité de lecture |
Oui
|
Vulgarisation |
Non
|
Nom de la revue |
|
Langue du document |
Anglais
|
Audience |
Internationale
|
Date de publication |
2020-12
|
Volume |
10
|
Numéro |
1
|
Domaine(s) |
|
DOI | 10.1038/s41598-020-65988-w |
Pubmed Id | 32494000 |
PubMed Central | PMC7271195 |
Origine :
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