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Publications de l’équipe
Regulation spatio temporelle de la présentation des antigènes et
migration cellulaire
Année de publication : 2008
Gabrielle Faure-André, Pablo Vargas, Maria-Isabel Yuseff, Mélina Heuzé, Jheimmy Diaz, Danielle
Lankar, Veronica Steri, Jeremy Manry, Stéphanie Hugues, Fulvia Vascotto, Jérôme Boulanger,
Graça Raposo, Maria-Rosa Bono, Mario Rosemblatt, Matthieu Piel, Ana-Maria Lennon-Duménil
(2008 Dec 17)
Regulation of dendritic cell migration by CD74, the MHC class II-associated
invariant chain.
Science (New York, N.Y.) : 1705-10 : DOI : 10.1126/science.1159894
Résumé
Dendritic cells (DCs) sample peripheral tissues of the body in search of antigens to present
to T cells. This requires two processes, antigen processing and cell motility, originally
thought to occur independently. We found that the major histocompatibility complex IIassociated invariant chain (Ii or CD74), a known regulator of antigen processing, negatively
regulates DC motility in vivo. By using microfabricated channels to mimic the confined
environment of peripheral tissues, we found that wild-type DCs alternate between high and
low motility, whereas Ii-deficient cells moved in a faster and more uniform manner. The
regulation of cell motility by Ii depended on the actin-based motor protein myosin II.
Coupling antigen processing and cell motility may enable DCs to more efficiently detect and
process antigens within a defined space.
R J Hawkins, M Piel, G Faure-Andre, A M Lennon-Dumenil, J F Joanny, J Prost, R Voituriez (2008
Sep 18)
Pushing off the walls: a mechanism of cell motility in confinement.
Physical review letters : 058103
Résumé
We propose a novel mechanism of cell motility, which relies on the coupling of actin
polymerization at the cell membrane to geometric confinement. We consider a polymerizing
viscoelastic cytoskeletal gel confined in a narrow channel, and show analytically that
spontaneous motion occurs. Interestingly, this does not require specific adhesion with the
channel walls, and yields velocities potentially larger than the polymerization velocity. The
contractile activity of myosin motors is not necessary to trigger motility in this mechanism,
but is shown quantitatively to increase the velocity. Our model qualitatively accounts for
recent experiments which show that cells without specific adhesion proteins are motile only
in confined environments while they are unable to move on a flat surface, and could help in
understanding the mechanisms of cell migration in more complex confined geometries such
as living tissues.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Publications de l’équipe
Regulation spatio temporelle de la présentation des antigènes et
migration cellulaire
Année de publication : 2007
Delphine Le Roux, Danielle Lankar, Maria-Isabel Yuseff, Fulvia Vascotto, Takeaki Yokozeki,
Gabrielle Faure-André, Evelyne Mougneau, Nicolas Glaichenhaus, Bénédicte Manoury, Christian
Bonnerot, Ana-Maria Lennon-Duménil (2007 Jun 29)
Syk-dependent actin dynamics regulate endocytic trafficking and processing of
antigens internalized through the B-cell receptor.
Molecular biology of the cell : 3451-62
Résumé
Antigen binding to the B-cell receptor (BCR) induces multiple signaling cascades that
ultimately lead to B lymphocyte activation. In addition, the BCR regulates the key trafficking
events that allow the antigen to reach endocytic compartments devoted to antigen
processing, i.e., that are enriched for major histocompatibility factor class II (MHC II) and
accessory molecules such as H2-DM. Here, we analyze the role in antigen processing and
presentation of the tyrosine kinase Syk, which is activated upon BCR engagement. We show
that convergence of MHC II- and H2-DM-containing compartments with the vesicles that
transport BCR-uptaken antigens is impaired in cells lacking Syk activity. This defect in
endocytic trafficking compromises the ability of Syk-deficient cells to form MHC II-peptide
complexes from BCR-internalized antigens. Altered endocytic trafficking is associated to a
failure of Syk-deficient cells to properly reorganize their actin cytoskeleton in response to
BCR engagement. We propose that, by modulating the actin dynamics induced upon BCR
stimulation, Syk regulates the positioning and transport of the vesicles that carry the
molecules required for antigen processing and presentation.
Fulvia Vascotto, Danielle Lankar, Gabrielle Faure-André, Pablo Vargas, Jheimmy Diaz, Delphine
Le Roux, Maria-Isabel Yuseff, Jean-Baptiste Sibarita, Marianne Boes, Graça Raposo, Evelyne
Mougneau, Nicolas Glaichenhaus, Christian Bonnerot, Bénédicte Manoury, Ana-Maria LennonDuménil (2007 Mar 29)
The actin-based motor protein myosin II regulates MHC class II trafficking and
BCR-driven antigen presentation.
The Journal of cell biology : 1007-19
Résumé
Antigen (Ag) capture and presentation onto major histocompatibility complex (MHC) class II
molecules by B lymphocytes is mediated by their surface Ag receptor (B cell receptor [BCR]).
Therefore, the transport of vesicles that carry MHC class II and BCR-Ag complexes must be
coordinated for them to converge for processing. In this study, we identify the actinassociated motor protein myosin II as being essential for this process. Myosin II is activated
upon BCR engagement and associates with MHC class II-invariant chain complexes. Myosin II
inhibition or depletion compromises the convergence and concentration of MHC class II and
BCR-Ag complexes into lysosomes devoted to Ag processing. Accordingly, the formation of
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2
Publications de l’équipe
Regulation spatio temporelle de la présentation des antigènes et
migration cellulaire
MHC class II-peptides and subsequent CD4 T cell activation are impaired in cells lacking
myosin II activity. Therefore, myosin II emerges as a key motor protein in BCR-driven Ag
processing and presentation.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3