PXD047515-2

PXD047515 is an original dataset announced via ProteomeXchange.

Title	Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment
Description	Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we utilize UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding for proteins known to interact with postsynaptic AMPA and NMDA receptors. Loci in/near Discs Large Homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P<5x10-8) for BF% and/or BMI. To further evaluate the functional role of PSD-95 (gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PDZ-domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising new therapeutic avenue for sustained weight loss.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:57.046.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Wierer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-04 16:21:28	ID requested
1	2024-06-16 04:31:11	announced
⏵ 2	2024-10-22 06:45:58	announced	2024-10-22: Updated project metadata.

10.1126/sciadv.adg2636;

Fadahunsi N, Petersen J, Metz S, Jakobsen A, Vad Mathiesen C, Silke Buch-Rasmussen A, Kurgan N, Kj, æ, rgaard Larsen J, Andersen RC, Topilko T, Svendsen C, Apuschkin M, Skovbjerg G, Hendrik Schmidt J, Houser G, Elgaard Jager S, Bach A, Deshmukh AS, Kilpel, ä, inen TO, Str, ø, mgaard K, Madsen KL, Clemmensen C, Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment. Sci Adv, 10(9):eadg2636(2024) [pubmed]

submitter keyword: weight-loss,brain

Christoffer Clemmensen
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen Blegdamsvej 3B, 2200-Copenhagen, Denmark
contact email	chc@sund.ku.dk
lab head
Michael Wierer
contact affiliation	Proteomics Research Infrastructure, University of Copenhagen
contact email	michael.wierer@sund.ku.dk
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/2024/06/PXD047515

PRIDE project URI

• PRIDE
  1. PXD047515
     1. Label: PRIDE project
     2. Name: Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment