Membrane Traffic in Neuronal and Epithelial Morphogenesis

Membrane trafficking allows for the communication between the different membrane compartments of the biosynthetic and endocytic pathways and for the communication between cells and their environment through the secretion of signalling molecules by exocytosis and capture of nutrients by endocytosis. Exocytosis and endocytosis are crucial to maintain cell homeostasis and are also involved in differentiation and morphogenesis of cells.

Neuronal cell differentiation and de-differentiation of epithelial into mesenchymal cells represent two fundamental models of important cellular changes in shape and function. These two processes share common principles because both imply the presence of a domain specialized for cell movement at the leading edge of the cell, the axonal growth cone and the pseudopodium respectively.

Our working hypothesis is that exocytosis is responsible for the release and expression at the plasma membrane of proteins that are important for cell migration, outgrowth of axons and dendrites, attachment to the extracellular matrix, formation and maintenance of synapses, and the repair and plasticity of neuronal and epithelial cells.

The aim of the team is to understand the basic mechanisms and the regulation of membrane trafficking in axonal outgrowth and epithelial cell migration. We study the function the vesicular SNAREs Cellubrevin, Synaptobrevin and TI-VAMP at the molecular, cellular and organism level. We also study Vezatin, an adhesion protein associated to the actin-based cytoskeleton, in dynamic processes of the central nervous system, our ultimate goal being to contribute to link human disorders to structural defects.

We use classical techniques of cellular and molecular biology with special emphasis on live cell imaging and proteomics, as well as biophysical approaches to study membrane dynamics, adhesion and fusion in vitro. Our models include mutant mice, cultured neuronal and epithelial cells, and the reconstitution of proteins into artificial membranes.

 

Hippocampal neuron. Acetylated (green) and tyrosinated (red) tubulin.

Selection of publications

Ji H, Coleman J, Yang R, Melia TJ, Rothman JE, Tareste D.
Protein determinants of SNARE-mediated lipid mixing.
Biophys J. 2010 Jul 21;99(2):553-60. 
Abstract
 
Danglot L, Chaineau M, Dahan M, Gendron MC, Boggetto N, Perez F, Galli T.
Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling.
J Cell Sci. 2010 Mar 1;123(Pt 5):723-35. Epub 2010 Feb 9.
FREE Full Text
 
Burgo A, Sotirakis E, Simmler MC, Verraes A, Chamot C, Simpson JC, Lanzetti L, Proux-Gillardeaux V, Galli T.
Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth.
EMBO Rep. 2009 Oct;10(10):1117-24. Epub 2009 Sep 11.
Abstract

Bahloul* A, Simmler* MC, Michel V, Leibovici M, Perfettini I, Roux I, Weil D, Nouaille S, Zuo J, Zadro C, Licastro D, Gasparini P, Avan P, Hardelin JP, Petit C.
Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells. *: co-1st authors.
EMBO Mol Med. 2009 May;1(2):125-38.
Abstract

Proux-Gillardeaux V, Gavard J, Irinopoulou T, Mège RM, Galli T.
Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell migration and integrin-dependent cell adhesion.
Proc Natl Acad Sci U S A. 2005 May 3;102(18):6362-7. Epub 2005 Apr 25.
FREE Full Text

Last modified 03/14/2011

Top