|Our group studies the dynamics of intracellular membranes in developing and mature neurons, in healthy and pathogenic contexts. Dysfunction of intracellular endosomal and mitochondrial dynamics has been linked to a variety of psychiatric including depression and schizophrenia and neurodegenerative disorders, including Charcot-Marie-Tooth (CMT), Alzheimer, Parkinson and Huntington diseases. This certainly suggests a crucial role of membrane dynamics in the formation and maintenance of neuronal elaborated shapes and contacts. Despite a large amount of literature, the molecular and cellular principles that govern the establishment and maintenance of neuronal shapes and contacts (synapses) still remain to be elucidated.
Massive membrane expansion during development and maintenance of large cell surface area during life require continuous addition of new membrane. Our recent work has shown that close contacts between the ER, where most lipids are synthesized, and the PM also play a role in neurite growth through non-vesicular lipid transfer. Which types of secretory vesicles are involved and how non-vesicular mechanisms participate to membrane expansion is not clear at all. How the neuronal membranes are maintained during life and aging and how the underlying mechanisms may be impaired in neurodegeneration are still open questions.
The aim of the team is to understand the basic mechanisms and the regulation of membrane trafficking in the context of brain development, psychiatric diseases, brain tumors and neurodegeneration (Parkinson, Alzheimer). We use 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.
5 MAIN PUBLICATIONS
Maja Petkovic, Aymen Jemaiel, Frédéric Daste, Christian G. Specht, Ignacio Izeddin, Daniela Vorkel, Jean-Marc Verbavatz, Xavier Darzacq, Antoine Triller, Karl H. Pfenninger, David Tareste, Catherine L. Jackson & Thierry Galli (2014)
The SNARE Sec22b has a non-fusogenic function in plasma membrane expansion
Nature Cell Biology 16, 434–444 (2014)
Paola Larghi, David J Williamson, Jean-Marie Carpier, Stéphanie Dogniaux, Karine Chemin, Armelle Bohineust, Lydia Danglot, Katharina Gaus, Thierry Galli & Claire Hivroz (2013)
VAMP7 controls T cell activation by regulating the recruitment and phosphorylation of vesicular Lat at TCR-activation sites
Nature Immunology 14, 723–731
Burgo A., Proux-Gillardeaux, V., Sotirakis, E., Bun, P., Casano,A., Verraes, A., Liem, R., Formstecher, E., Coppey-Moisan, M. Galli, T. (2012).
A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery.
Dev Cell 23:166-180
Danglot L, Zylbersztejn K, Petkovic M, Meziane H, Combe R, Champy Mf, Birling Mc, Pavlovic G, Bizot Jc, Trovero F, Della Ragione F, Proux-Gillardeaux V, Sorg T, D’esposito M, Galli T. (2012).
Absence of TI-VAMP/Vamp7 leads to increased anxiety in mice.
J Neurosci 32:1962-1968. (Comment in Faculty of 1000: 6)
Zylbersztejn K, Petkovic M, Burgo A, Deck M, Garel S, Marcos S, Bloch-Gallego E, Nothias F, Serini G, Bagnard D, Binz T, Galli T. (2012).
The vesicular SNARE Synaptobrevin is required for Semaphorin 3A axonal repulsion.
J Cell Biol 196:37-46. (Comment in Faculty of 1000: 8)