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Publications de l’équipe
Dynamique de la membrane et du cytosquelette
Année de publication : 2014
Guillaume Montagnac, Philippe Chavrier (2014 Feb 28)
[When microtubules meet clathrin-coated pits].
Mé decine sciences : M/S : 130-3 : DOI : 10.1051/medsci/20143002005
Résumé
Année de publication : 2013
Pedro Monteiro, Carine Rossé, Antonio Castro-Castro, Marie Irondelle, Emilie Lagoutte, Perrine
Paul-Gilloteaux, Claire Desnos, Etienne Formstecher, François Darchen, David Perrais, Alexis
Gautreau, Maud Hertzog, Philippe Chavrier (2013 Dec 18)
Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at
invadopodia.
The Journal of cell biology : 1063-79
Résumé
Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination
requires formation of actin-based protrusions of the plasma membrane called invadopodia,
where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here,
we describe an interaction between the exocyst complex and the endosomal Arp2/3
activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and
exocyst are required for matrix degradation by an exocytic mechanism that involves tubular
connections between MT1-MMP–positive late endosomes and the plasma membrane in
contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular
matrix degradation and tumor cell invasion into different pathologically relevant matrix
environments. Our data suggest a general mechanism used by tumor cells to breach the
basement membrane and for invasive migration through fibrous collagen-enriched tissues
surrounding the tumor.
Maud Hertzog, Pedro Monteiro, Gaëlle Le Dez, Philippe Chavrier (2013 Jan 10)
Exo70 subunit of the exocyst complex is involved in adhesion-dependent
trafficking of caveolin-1.
PloS one : e52627 : DOI : 10.1371/journal.pone.0052627
Résumé
Caveolae are specialized domains of the plasma membrane, which play key roles in
signaling, endocytosis and mechanosensing. Using total internal reflection fluorescent
microscopy (TIRF-M), we observe that the exocyst subunit Exo70 forms punctuate structures
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Publications de l’équipe
Dynamique de la membrane et du cytosquelette
at the plasma membrane and partially localizes with caveolin-1, the main component of
caveolae. Upon cell detachment, we found that Exo70 accumulates with caveolin-1-positive
vesicular structures. Upon cell re-adhesion, caveolin-1 traffics back to the plasma membrane
in a multistep process involving microtubules and actin cytoskeleton. In addition, silencing of
Exo70 redirects caveolin-1 to focal adhesions identified by markers such as α5 integrin or
vinculin. Based on these findings, we conclude that Exo70 is involved in caveolin-1 recycling
to the plasma membrane during re-adhesion of the cells to the substratum.
Année de publication : 2012
Antonio Castro-Castro, Carsten Janke, Guillaume Montagnac, Perrine Paul-Gilloteaux, Philippe
Chavrier (2012 Dec 9)
ATAT1/MEC-17 acetyltransferase and HDAC6 deacetylase control a balance of
acetylation of alpha-tubulin and cortactin and regulate MT1-MMP trafficking and
breast tumor cell invasion.
European journal of cell biology : 950-60 : DOI : 10.1016/j.ejcb.2012.07.001
Résumé
Invasive tumor cells use proteases to degrade and migrate through the stromal environment
consisting of a 3D network of extracellular matrix macromolecules. In particular, MT1-MMP, a
membrane-anchored metalloproteinase, is critical during cancer cell invasion. MT1-MMP is
stored in endosomal compartments and then delivered to invadopodia, the specialized
plasma membrane domains of invasive cancer cells endowed with extracellular matrixdegradation capacity. In macrophages, traffic of MT1-MMP vesicles to invadopodia-related
podosomes requires microtubules. We previously found that in breast tumor MDA-MB-231
cells an increase of microtubule and cortactin acetylation upon inhibition of HDAC6
correlates with a decrease of matrix degradation and invasion in three-dimensional collagen I
gel. Here, we investigated the role of the recently identified α-tubulin N-acetyltransferase 1
ATAT1 in invasive MDA-MB-231 cells. We found that the dynamics and distribution of MT1MMP-positive endosomes require regulation of acetylation levels. We observed that ATAT1
tubulin acetyltransferase binds and regulates cortactin acetylation levels. In addition, ATAT1
colocalizes with cortactin at the adherent surface of the cells and it is required for 2D
migration and invasive migration of MDA-MB-231 cells in collagen matrix. All together, our
data indicate that a balance of acetylation and deaceylation by ATAT1/HDAC6 enzymes with
opposite activities regulates the migratory and invasive capacities of breast tumor cells.
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