Rôle de la modification des lipides dans la biogenèse de vésicules et la fission Role of lipid modifications in vesicle biogenesis and fission

Résumé

Dans la cellule eucaryote, le transport intracytoplasmique entre les différents compartiments s’effectue généralement par l’intermédiaire d’organites individualisés, le plus souvent sous forme de vésicules. La formation de ces vésicules, leur transport et la fusion avec un compartiment cible nécessitent l’action de protéines cytosoliques dont l’identité varie en fonction de leurs constituants moléculaires ainsi que des compartiments d’origine et de destination. Certaines de ces protéines participent plus spécifiquement aux différentes étapes de la formation d’une vésicule, le recrutement des protéines transmembranaires, l’assemblage d’un manteau contribuant aux contraintes physiques nécessaires au bourgeonnement et la fission. L’interaction de ces protéines avec la face cytosolique de la bicouche lipidique nécessite un contrôle à la fois spatial et temporel. Ce contrôle est principalement assuré par la modification de certains lipides membranaires qui contrôlent toutes les étapes de la formation d’une vésicule ainsi que sa fusion avec la membrane cible.

Summary

Vesicular traffic is essential for the maintenance of cellular functions as well as inter-cellular communication. Sequential steps of vesicular traffic require the action of cytosolic proteins that are involved in spatial and temporal control of budding, fission, vectorial transport, and fusion with the target compartment. Some of these proteins have been identified as lipid-modifying enzymes that regulate vesicular traffic from, and between the different compartments in the cell. Phosphorylated derivatives of phosphatidylinositol are the most widely used membrane lipids that are acting as specific recruitors and activators of cytosolic proteins among which the members of vesicular coats, proteins that are involved in the regulation of actin dynamics as well as other enzymes involved in lipid metabolism. Here are described, in particular, the roles of phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate, two of the most relevant phospho-inositides involved in sequential steps of vesicular budding and fission, from both the Golgi apparatus and the plasma membrane. In addition, this review presents new concepts on the mechanism of action of cytosolic proteins that are binding to, and catalyzing the formation of, acidic membrane lipids. By doing so, these proteins may contribute, through biophysical principles that still remain to be determined and are discussed here, to deform the target membrane, hence promoting membrane budding and fission.