Six scissors: regulation of ADAM10 by tetraspanins

The molecular scissor ADAM10 is critical for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammation. ADAM10 functions by cleaving the extracellular regions from substrates including Notch cell-fate regulators, cadherin adhesion molecules and amyloid precursor protein. We recently proposed the ‘six scissor’ hypothesis, whereby ADAM10 is not one scissor, but six different scissors with different substrate specificities. This is dictated by ADAM10 association with one of six regulatory tetraspanin membrane proteins. In future, it may be possible to treat human diseases by targetting individual tetraspanins, avoiding the toxicity of targetting ADAM10 on every cell in the body.