CV Science

Nicolas Vitale PhD in Neurosciences and Cell biology

Course and current status

ORCID ID : 0000 0002 4752 4907

-  From 2010: Editor Scientific Reports

 -  From 2006: DR2 INSERM.

Editorial Board member of the Journal of Biological Chemistry (2003-2022), Frontiers in Neuroendocrine Sciences and Current Chemical Biology.

- 2003 : HRD Université Louis Pasteur de Strasbourg.

- 1997 : CR2 INSERM at the U-338 INSERM (Dir. Dominique Aunis)

- 1997-1995 : postdoctoral position in the Pulmonary-Critical Care Medicine Branch, National Heart, Lung and Blood Institute of the National Institute of Health à Bethesda (Dir. Joel Moss). Fellowship INSERM, then Fogarty.

- 1994-1992 : PhD under the supervision of Marie-France Bader. Teaching at the Faculty of Medicine of Strasbourg.

PRIZES

1997-1998: Best posters at two Keystone Symposia (USA)

1998: FARE award, National Institutes of Health, Bethesda, Maryland (USA).

2003: Best communication at the EMBO workshop, Cargèse (France).

2007: Prize from the "Fédération pour la Recherche Médicale".

2008 : Prize Guy Ourisson, from the Cercle Gutenberg.

2010-2013 : Prime d'Excellence Scientifique INSERM

Aurélie Béglé (2009), Mohamed Ammar (2013), and Emeline Tanguy (2020) were awarded of PhD prices from the Société de Biologie de Strasbourg.

Emeline Tanguy was awarded in 2020 of a PhD price from the Groupe d’Etude et de Recherche en Lipidomique (GERLI).

GRANTS

PI on an ANR-Blanc (2005-2008)

PI on an ARC grant (2007-2009)

FRM prix région Alsace (2007)

PI on an ANR-Blanc (2009-2011)

PI on several grants from the Ligue Contre le Cancer (2010-2017)

PI on a FRM grant (2016-2019)

PI on an ANR grant (2020-2024)

Scientific summary

Cells control very precisely their three-dimensional organization and to do so, they have developed specialized subcellular compartments. For instance, vesicular structures assure the transport of specific molecules from one part of the cell to another. To maintain cellular homeostasis, the distribution and composition of these structures are very tightly regulated. Hence, most cellular activities including cell communication, defense and migration involve vesicular trafficking steps, which end by the fusion of distinct membrane compartments. Despite a fundamental mechanism that appears very similar (i.e. the fusion between two lipid bi-layers), the kinetics and spatial and temporal regulation of these different processes vary greatly (from milliseconds for neurotransmitter release to minutes for phagocytosis), arguing for essential differences in the underlying mechanisms.

To date, most of our knowledge of the molecular machinery underlying membrane fusion is related to proteins. For instance, SNAREs and accessory proteins have been found to be critical for pulling membranes together and rendering them fusion competent (Jahn and Scheller, 2006). Because membrane fusion involves above all merging of two membranes it appears likely that lipids are essential partners for proteins in the basic fusogenic machinery (for review see Zeniou-Meyer et al., 2006). On the other hand, the membrane lipid organization and the signaling lipids required for the late stages of membrane fusion remain poorly understood.

Phosphatidic acid (PA) synthesized by phospholipase D (PLD) appears an attractive candidate to promote membrane fusion because PA is a multifunctional lipid that has been proposed to serve as a protein attachment site (Liscovitch et al., 2000), to activate selected enzymes (Honda et al., 1999) and lastly to alter membrane curvature (Koojman et al., 2005), all of which are of particular interest in the context of vesicular trafficking and membrane fusion. However up to recently, most studies focusing on the role of lipids in membrane fusion have used in vitro assays.

In support of the hypothesis that PA is critical to membrane fusion, PLD enzymes are generally located on membranes undergoing active fusion (for review Zeniou-Meyer et al., 2006). Accordingly, several recent functional studies based on the use of inhibitors, dominant-negative mutants and RNA interference support a role for PLD in membrane fusion (for review see Bader and Vitale, 2008). Funded by previous ANR grants, we have demonstrated that PA synthesis by PLD is critical for membrane fusion in different cellular processes and cell types (Wasselle et al., 2005; Corrotte et al., 2006; Zeniou-Meyer et al., 2007, Diesse et al., 2008). In addition, we have shown that the SNARE protein Syntaxin-1 requires binding to PA to promote secretory granule exocytosis (Lam et al., 2008), in line with the idea that changes in membrane topology induced by the local accumulation of PA at the vesicle docking site act synergistically with SNARE proteins to promote membrane fusion. In agreement with the general concept of PA-driven membrane fusion, PA has been also recently shown to be critical for membrane fusion of intracellular organelles such as mitochondria and the Golgi apparatus (Choi et al., 2006; Yang et al., 2008). These different observations suggest that among the fusogenic lipids PA plays a prominent role in various membrane fusion events. More recently, using transgenic mice models, pharmacological approaches associated with lipidomics analysis, we have shown that different species of PA are synthesized during exocytosis (Tanguy et al., 2020). In fact, mono-unsaturated  PA levels at the vesicular docking sites appear to control the number of exocytotic events while polyunsaturated PA control the kinetics of the fusion pore, highlighting the contribution of several PA species in regulated exocytosis (Tanguy et al., 2020). We are currently developing novel optogenetic and optical tools to modulate more precisely PA levels in specific membrane compartments and in timely controlled manner. These tools should be helpfull to study the many fonctions of PA in regulated exocytosis, but also in many other cellular processes.