Cover Image

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

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is als...

Full description

Saved in:
Bibliographic Details
Main Authors: Kuhn, Peer-Hendrik (Author) , Colombo, Alessio Vittorio (Author) , Schusser, Benjamin (Author) , Yildiz, Daniela (Author) , Wetzel, Sebastian (Author) , Schepers, Ute (Author) , Herber, Julia (Author) , Ludwig, Andreas (Author) , Kremmer, Elisabeth (Author) , Montag, Dirk (Author) , Müller, Ulrike C. (Author) , Schweizer, Michaela (Author) , Saftig, Paul (Author) , Bräse, Stefan (Author) , Lichtenthaler, Stefan F (Author)
Format: Article (Journal)
Language:English
Published: 23 January 2016
In: eLife
Year: 2016, Volume: 5, Pages: 1-29
ISSN:2050-084X
DOI:10.7554/eLife.12748
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.12748
Get full text
Author Notes:Peer-Hendrik Kuhn, Alessio Vittorio Colombo, 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 Lichtenthaler
Description
Summary:Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain.
Item Description:Gesehen am 03.06.2020
Physical Description:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.12748

Similar Items