Notch receptor-ligand interactions during T cell development, a ligand endocytosis-driven mechanism

Notch signaling plays an important role during the development of different cell types and tissues. The role of Notch signaling in lymphocyte development, in particular in the development and commitment to the T cell lineage, has been the focus of research for many years. Notch signaling is absolutely required during the commitment and early stages of T cell development. Activation of the Notch signaling pathway is initiated by ligand-receptor interactions and appears to require active endocytosis of Notch ligands. Studies addressing the mechanism underlying endocytosis of Notch ligands have helped to identify the main players important and necessary for this process. Here, we review the Notch ligands, and the proposed models of Notch activation by Notch ligand endocytosis, highlighting key molecules involved. In particular, we discuss recent studies on Notch ligands involved in T cell development, current studies aimed at elucidating the relevance of Notch ligand endocytosis during T cell development and the identification of key players necessary for ligand endocytosis in the thymus and during T cell development.