Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

• DOI: 10.7554/elife.12748
• Publication Date: 2016-01-23T12:46:28Z
• Authors: Peer-Hendrik Kuhn; Alessio Vittorio ...; Benjamin Schusser; Daniela Dreymueller; Sebastian Wetzel; Ute Schepers; Julia Herber; Andreas Ludwig; Elisabeth Kremmer; Dirk Montag; Ulrike Müller; Michaela Schweizer; Paul Saftig; Stefan Bräse; Stefan F Lichtent...
• Keywords: ADAM10

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One proteases is a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase Alzheimer's disease amyloid precursor protein. ADAM10 also required for neuronal network functions murine brain, but substrates are only partly known. With a proteomic analysis Adam10-deficient neurons we identified 91, mostly novel substrate candidates, making protease proteins nervous system. Several substrates, including cell adhesion protein NrCAM, involved brain development. Indeed, detected mistargeted axons olfactory bulb conditional ADAM10-/- mice, correlate with reduced cleavage NCAM and other substrates. In summary, provide molecular basis dysfunctions mice demonstrate fundamental brain.