Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding

Metalloprotease-disintegrins (ADAMs) have captured our attention as key pla yers in fertilization and in the processing of the ectodomains of proteins such as tumor necrosis factor alpha (TNF alpha), and because of their roles in Notch-mediated signaling, neurogenesis and muscle fusion. ADAMs are int egral membrane glycoproteins that contain a disintegrin domain, which is re lated to snake-venom integrin ligands, and a metalloprotease domain (which can contain or lack a catalytic site). Here, we review and critically discu ss current topics in the ADAMs field, including the central role of fertili n in fertilization, the role of the TNF alpha convertase in protein ectodom ain processing, the role of Kuzbanian in Notch signaling, and links between ADAMs and processing of the amyloid-precursor protein.