PXD003426

PXD003426 is an original dataset announced via ProteomeXchange.

Title	Systematic substrate identification reveals a central role for the metalloprotease ADAM10 in axon targeting and synapse function
Description	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 potential molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 as a sheddase in the brain.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:27:48.284.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peer-Hendrik Kuhn
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-06 01:50:26	ID requested
1	2018-10-17 20:16:49	announced
⏵ 2	2024-10-22 04:27:56	announced	2024-10-22: Updated project metadata.

Kuhn PH, Colombo AV, Schusser B, Dreymueller D, Wetzel S, Schepers U, Herber J, Ludwig A, Kremmer E, Montag D, M, ü, ller U, Schweizer M, Saftig P, Br, ä, se S, Lichtenthaler SF, Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function. Elife, 5():(2016) [pubmed]

10.7554/eLife.12748;

curator keyword: Biomedical

submitter keyword: neurons,ADAM10 substrates, protease, bioorthogonal chemistry

Prof. Dr. Stefan F. Lichtenthaler
contact affiliation	Lehrstuhl für Neuroproteomik, Technische Universität München und Neuroproteomik, Deutsches Zentrum für Neurodegenerative Erkrankungen, München
contact email	Stefan.Lichtenthaler@dzne.de
lab head
Peer-Hendrik Kuhn
contact affiliation	DZNE München
contact email	peerhendrik@gmx.net
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD003426

PRIDE project URI

• PRIDE
  1. PXD003426
     1. Label: PRIDE project
     2. Name: Systematic substrate identification reveals a central role for the metalloprotease ADAM10 in axon targeting and synapse function