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Team Publications
Membrane and Cytoskeleton Dynamics
Year of publication 2008
Anika Steffen, Gaëlle Le Dez, Renaud Poincloux, Chiara Recchi, Pierre Nassoy, Klemens Rottner,
Thierry Galli, Philippe Chavrier (2008 Jun 24)
MT1-MMP-dependent invasion is regulated by TI-VAMP/VAMP7.
Current biology : CB : 926-31 : DOI : 10.1016/j.cub.2008.05.044
Summary
Proteolytic degradation of the extracellular matrix (ECM) is one intrinsic property of
metastatic tumor cells to breach tissue barriers and to disseminate into different tissues.
This process is initiated by the formation of invadopodia, which are actin-driven, finger-like
membrane protrusions. Yet, little is known on how invadopodia are endowed with the
functional machinery of proteolytic enzymes [1, 2]. The key protease MT1-MMP (membrane
type 1-matrix metalloproteinase) confers proteolytic activity to invadopodia and thus
invasion capacity of cancer cells [3-6]. Here, we report that MT1-MMP-dependent matrix
degradation at invadopodia is regulated by the v-SNARE TI-VAMP/VAMP7, hence providing
the molecular inventory mediating focal degradative activity of cancer cells. As observed by
TIRF microscopy, MT1-MMP-mCherry and GFP-VAMP7 were simultaneously detected at
proteolytic sites. Functional ablation of VAMP7 decreased the ability of breast cancer cells to
degrade and invade in a MT1-MMP-dependent fashion. Moreover, the number of invadopodia
was dramatically decreased in VAMP7- and MT1-MMP-depleted cells, indicative of a positivefeedback loop in which the protease as a cargo of VAMP7-targeted transport vesicles
regulates maturation of invadopodia. Collectively, these data point to a specific role of
VAMP7 in delivering MT1-MMP to sites of degradation, maintaining the functional machinery
required for invasion.
Mika Sakurai-Yageta, Chiara Recchi, Gaëlle Le Dez, Jean-Baptiste Sibarita, Laurent Daviet,
Jacques Camonis, Crislyn D'Souza-Schorey, Philippe Chavrier (2008 Jun 11)
The interaction of IQGAP1 with the exocyst complex is required for tumor cell
invasion downstream of Cdc42 and RhoA.
The Journal of cell biology : 985-98 : DOI : 10.1083/jcb.200709076
Summary
Invadopodia are actin-based membrane protrusions formed at contact sites between
invasive tumor cells and the extracellular matrix with matrix proteolytic activity. Actin
regulatory proteins participate in invadopodia formation, whereas matrix degradation
requires metalloproteinases (MMPs) targeted to invadopodia. In this study, we show that the
vesicle-tethering exocyst complex is required for matrix proteolysis and invasion of breast
carcinoma cells. We demonstrate that the exocyst subunits Sec3 and Sec8 interact with the
polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA,
which are essential for matrix degradation. Interaction between IQGAP1 and the exocyst is
necessary for invadopodia activity because enhancement of matrix degradation induced by
the expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We further show
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Team Publications
Membrane and Cytoskeleton Dynamics
that the exocyst and IQGAP1 are required for the accumulation of cell surface membrane
type 1 MMP at invadopodia. Based on these results, we propose that invadopodia function in
tumor cells relies on the coordination of cytoskeletal assembly and exocytosis downstream
of Rho guanosine triphosphatases.
Guillaume Montagnac, Philippe Chavrier (2008 May 17)
Endosome positioning during cytokinesis.
Biochemical Society transactions : 442-3 : DOI : 10.1042/BST0360442
Summary
In mammalian cells, completion of cytokinesis relies on targeted delivery of recycling
membranes to the midbody. At this step of mitosis, recycling endosomes are organized as
clusters located at the mitotic spindle poles as well as at both sides of the midbody.
However, the mechanism that controls endosome positioning during cytokinesis is not
known. Here, we discuss the possible mechanisms that drive the formation of endosomal
clusters and the importance of this process for the targeted delivery of recycling membranes
to the midbody.
Guillaume Montagnac, Arnaud Echard, Philippe Chavrier (2008 May 13)
Endocytic traffic in animal cell cytokinesis.
Current opinion in cell biology : 454-61 : DOI : 10.1016/j.ceb.2008.03.011
Summary
Cytokinesis is the final step of mitosis whereby two daughter cells physically separate. It is
initiated by the assembly of an actomyosin contractile ring at the mitotic cell equator, which
constricts the cytoplasm between the two reforming nuclei resulting in the formation of a
narrow intercellular bridge filled with central spindle microtubule bundles. Cytokinesis
terminates with the cleavage of the intercellular bridge in a poorly understood process called
abscission. Recent work has highlighted the importance of membrane trafficking events
occurring from membrane compartments flanking the bridge to the central midbody region.
In particular, polarized delivery of endocytic recycling membranes is essential for completion
of animal cell cytokinesis. Why endocytic traffic occurs within the intercellular bridge remains
largely mysterious and its significance for cytokinesis will be discussed.
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