PXD051088-1

PXD051088 is an original dataset announced via ProteomeXchange.

Title	DEP-1 is a novel brain insulin receptor phosphatase and disallows the development of futile cycles
Description	A healthy metabolism relies on the precise regulation of anabolic and catabolic pathways. Insulin and AMPK serve as key regulators of anabolism and catabolism, respectively. While insulin deficiency markedly impairs anabolism, insulin resistance in obesity leads to metabolic dysfunction especially via altered brain insulin receptor activity. Density-enhanced phosphatase-1 (DEP-1), a ubiquitously expressed receptor-like tyrosine phosphatase, has been described as an insulin receptor phosphatase in peripheral tissues. Strikingly, diet-induced obese mice exhibit elevated DEP-1 expression in the brain. This study uncovers DEP-1's role in brain insulin signaling and its impact on ana- and catabolic pathways. Neurons lacking DEP-1 exhibit heightened insulin receptor phosphorylation and downstream signaling upon acute insulin stimulation. Surprisingly, this is accompanied by simultaneous activation of the AMPK cascade due to increased phospholipase C gamma 1 signaling. These opposing pathways in male DEP-1 forebrain/hippocampus-specific knockout mice result in heightened lipolysis in white adipose tissue, and enhanced fat oxidation in brown adipose tissue due to elevated sympathetic activation and enhanced beta-adrenergic receptor expression.
HostingRepository	PRIDE
AnnounceDate	2024-11-27
AnnouncementXML	Submission_2024-11-27_09:31:11.161.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luisa Marie Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-29 05:48:05	ID requested
⏵ 1	2024-11-27 09:31:12	announced

Chopra S, Kadiri OL, Ulke J, Hauffe R, Jonas W, Cheshmeh S, Schmidt L, Bishop CA, Yagoub S, Schell M, Rath M, Kr, ü, ger J, Lippert RN, Kr, ü, ger M, Kappert K, Kleinridders A, DEP-1 is a brain insulin receptor phosphatase that prevents the simultaneous activation of counteracting metabolic pathways. Cell Rep, 43(12):114984(2024) [pubmed]

10.1016/j.celrep.2024.114984;

submitter keyword: brain,insulin, DEP-1

André Kleinridders
contact affiliation	University of Potsdam, Institute of Nutritional Science, Molecular and Experimental Nutritional Medicine, Nuthetal, Germany
contact email	kleinridders@uni-potsdam.de
lab head
Luisa Marie Schmidt
contact affiliation	CECAD research center, Institue of Genetics, University of Cologne
contact email	luisa.schmidt@uni-koeln.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/2024/11/PXD051088

PRIDE project URI

• PRIDE
  1. PXD051088
     1. Label: PRIDE project
     2. Name: DEP-1 is a novel brain insulin receptor phosphatase and disallows the development of futile cycles