A growing family of Notch ligands

Signaling through Notch-like receptors is an evolutionarily well-conserved mechanism for cell-cell communication. Transmembrane ligands of the DSL (Delta, Serrate, LAG-2) family signal to Notch receptors on a neighboring cell, which results in an intracellular signaling cascade, influencing cellular differentiation. Recently published data shed new light on the repertoire of ligands and on processing of Notch receptors. One report provides evidence for a novel, more distantly related ligand of the Delta-type in mouse, Dll3 (Delta-like 3)¹. Ectopic expression of Dll3 perturbs primary neurogenesis in frog embryos in a manner expected for a bona fide Notch ligand. Two reports provide new information about processing of Notch receptors. A novel protease, Kuzbanian, is identified, which cleaves the Notch receptor at the extracellular side². Biochemical experiments show that the cleavage probably occurs during intracellular trafficking, and that only processed Notch receptors appear at the cell surface³. Taken together, these reports extend our knowledge about an important event in cell-cell communication—how Notch ligands and receptors meet and interact. BioEssays 20:103–107, 1998. © 1998 John Wiley & Sons, Inc.