Fonctions et régulation de l'activité de signalisation du récepteur Notch.

Abstract

Au cours du developpement, la mise en place des axes embryonnaires, des feuillets et des tissus depend de l' echange de divers signaux permettant aux cellules soit d' etablir et de maintenir des differences d' identite, soit a l' inverse de verifier et de renforcer leur identite commune. Ces quinze dernieres annees ont permis d' etablir que les voies de signalisation responsables de la transduction, de l' integration et de l' amplification de ces signaux sont peu nombreuses, mais conservees des invertebres aux mammiferes. Dans cette revue, l' etat actuel des connaissances concernant les fonctions du recepteur Notch sera presente, ainsi que l' analyse des mecanismes de transduction du signal et leur regulation.

Cell-cell interactions mediated by Notch play critical roles at multiple stages of development in both invertebrate and vertebrate species. Three types of Notch-dependent processes are illustrated in this review: lateral inhibition, binary fate decision following asymmetric cell division and formation of organization centers at compartmental boundaries. These last two processes illustrate how Notch activity can be modulated both at the cell surface and inside the cell. Notch signaling involves the interaction of the receptor with its ligand on an adjacent cell. This interaction appears to trigger an intracellular proteolytic cleavage that releases the intracellular domain of Notch. The activated form of the receptor is believed to enter the nucleus and promote transcription by interacting with the Suppressor of Hairless DNA-binding protein. The direct read-out of this signaling event is the transcriptional activation of Notch target-genes. [References: 33]