PXD012487

PXD012487 is an original dataset announced via ProteomeXchange.

Title	Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing
Description	GABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three interacting proteins, selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression. Proteomic and functional analyses revealed that APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor. Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to Aβ, a component of senile plaques in Alzheimer’s disease patients. Thus, APP/GBR complex formation links presynaptic GBR trafficking to Aβ formation. Our findings support that dysfunctional axonal trafficking and reduced GBR expression in Alzheimer’s disease increases Aβ formation.
HostingRepository	PRIDE
AnnounceDate	2019-11-13
AnnouncementXML	Submission_2019-11-12_18:05:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD012487
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Haupt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Phospho; Propionamide; Glu->pyro-Glu; Oxidation; Acetyl; Carbamidomethyl; Gln->pyro-Glu
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-24 00:34:32	ID requested
⏵ 1	2019-11-12 18:05:03	announced

Dinamarca MC, Raveh A, Schneider A, Fritzius T, Fr, ü, h S, Rem PD, Stawarski M, Lalanne T, Turecek R, Choo M, Besseyrias V, Bildl W, Bentrop D, Staufenbiel M, Gassmann M, Fakler B, Schwenk J, Bettler B, receptors links axonal trafficking to amyloidogenic processing. Nat Commun, 10(1):1331(2019) [pubmed]

curator keyword: Biological

submitter keyword: Cellular neuroscience, GABAB receptors, LC-MS/MS

Prof. Dr. Bernd Fakler
contact affiliation	Institute of Physiology II Universität Freiburg Germany
contact email	bernd.fakler@physiologie.uni-freiburg.de
lab head
Alexander Haupt
contact affiliation	University of Freiburg, Germany
contact email	alexander.haupt@physiologie.uni-freiburg.de
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/2019/11/PXD012487

PRIDE project URI

• PRIDE
  1. PXD012487
     1. Label: PRIDE project
     2. Name: Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing