Figure 1.

Six ADAM10 scissors: Tspan14 and Tspan5 may be important for Notch activation in immune cells. (A) A schematic representation of a TspanC8 and ADAM10. (B) A model figure to show the six different TspanC8/ADAM10 complexes, which have different subcellular localizations, distinct substrate specificities, and may have different ADAM10 conformations. Notch cleavage is initiated following engagement with a Notch ligand on another cell (1), which induces a conformational change that we hypothesize allows cleavage by a Tspan14/ADAM10 or Tspan5/ADAM10 scissor (2), followed by intramembrane cleavage by γ-secretase (3), to release the intracellular domain to act as a transcription factor and drive cell fate decisions (4). Tspan10 has also been implicated in Notch activation, but its relatively low expression by immune cells suggests no substantial role in these cells. N-linked and O-linked glycosylation sites are indicated by filled ovals and short lines, respectively.