The ADAM (A disintegrin and metalloprotease domain) family are membrane-anchored metalloproteases that mediate the proteolytic cleavage of many transmembrane proteins within their extracellular regions. This so-called ectodomain shedding plays an important role in many cell and developmental processes. ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons (Lammich et al. 1999, Kuhn et al. 2010), responsible for cleaving amyloid precursor protein (APP) in a non-amyloidogenic manner and producing APPs-alpha, a neuroprotective APP-derived peptide.
The trafficking of ADAM10 is regulated by a subgroup of the tetraspanin superfamily referred to as TspanC8 tetraspanins. TSPAN4, 14, 15 and 33 are thought to mediate ADAM10 exit from the ER and transport to the plasma membrane in a variety of ways (Noy et al. 2016, Jouannet et al. 2016).