Notch signaling pathway

Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Notch is present in all metazoans, and mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.[2] Notch signaling promotes proliferative signaling during neurogenesis and its activity is inhibited by Numb to promote neural differentiation.

The Notch protein spans the cell membrane, with part of it inside and part outside. Ligand proteins binding to the extracellular domain induce proteolytic cleavage and release of the intracellular domain, which enters the cell nucleus to modify gene expression. Because most ligands are also transmembrane proteins, the receptor is normally triggered only from direct cell-to-cell contact. In this way, groups of cells can organise themselves, such that, if one cell expresses a given trait, this may be switched off in neighbour cells by the intercellular notch signal. In this way, groups of cells influence one another to make large structures. Thus, lateral inhibition mechanisms are key to Notch signaling. The notch cascade consists of notch and notch ligands, as well as intracellular proteins transmitting the notch signal to the cell's nucleus. The Notch/Lin-12/Glp-1 receptor family[8] was found to be involved in the specification of cell fates during development in Drosophila and C. elegans.