Proteolytic Activation of Notch Signaling

Publisher Summary This chapter discusses potential roles for DSL ligand endocytosis in Notch signaling, with a focus on the generation of a physical force to mechanically dissociate and activate Notch. The Notch pathway is one of a relatively few signaling systems that is absolutely required for normal invertebrate and vertebrate development; however, Notch signaling also functions in the maintenance of adult cells and tissues. Signaling via the Notch pathway influences a wide range of cell types and cellular processes through effects on cell-type specification, differentiation, survival, proliferation, apoptosis, and morphogenetic events. Through a process known as lateral inhibition, Notch signaling restricts the selection of specific cell fates from a field of equivalent progenitors. However, Notch signaling induced between compartments of non-equivalent cells directs cell type specification and boundary formation required for tissue patterning and morphogenesis. Moreover, Notch signaling plays a critical role in coordinating binary cell-fate decisions obtained through asymmetric cell division, and losses in Notch signaling produce cell fate transformations. Finally, Notch signaling induced through interactions between stem cells and their adjacent niche cells has been implicated in stem cell survival, maintenance, and self-renewal, possibly reflecting a role for Notch in regeneration and renewal of tissues following injury and during aging in the adult.