PXD026225

PXD026225 is an original dataset announced via ProteomeXchange.

Title	Mass spectrometry-based analysis of the TBC1D4 interactome in human skeletal muscle
Description	Insulin-stimulated muscle glucose uptake is a key process to alleviate hyperglycemia. This process depends on the redistribution of glucose transporters to the muscle surface membrane following phosphorylation of TBC1D1 and TBC1D4. Genetic evidence from a TBC1D4 loss-of-function mutation in human skeletal muscle is associated with an increased risk of type 2 diabetes (T2D). However, little is known about the potential regulating interactors of TBC1D4 in skeletal muscle. Here, we sought to identify interactors of TBC1D4 in human skeletal muscle by an unbiased proteomics approach. We detected 76 proteins as candidate TBC1D4 interactors, whereof 12 were regulated by insulin stimulation including known proteins involved in glucose metabolism (e.g. 14-3-3 proteins and ACTN4). TBC1D1 also co-precipitated with TBC1D4 and vice versa in both human and mouse skeletal muscle. This interaction was not regulated by insulin or exercise in young healthy lean individuals. In contrast, we observed an altered interaction as well as compromised insulin-stimulated phospho-regulation of the TBC1D1-TBC1D4 complex in muscle of obese individuals with T2D. In conclusion, we provide a list of TBC1D4 interactors in human and mouse skeletal muscle. These protein interactors serve as potential regulators of TBC1D4 function and thus insulin-stimulated glucose uptake in skeletal muscle.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:10.686.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	atul shahaji deshmukh
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-24 06:38:57	ID requested
1	2022-03-01 00:09:12	announced
⏵ 2	2023-11-14 08:52:11	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Muscle, TBC1D4, Diabetes, Insulin, Interactome,LCMS

Atul S Deshmukh
contact affiliation	Novo Nordisk Center For Basic Metabolic Research, University of Copenhagen.
contact email	atul.deshmukh@sund.ku.dk
lab head
atul shahaji deshmukh
contact affiliation	Copenhagen University
contact email	atul.deshmukh@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026225
     1. Label: PRIDE project
     2. Name: Mass spectrometry-based analysis of the TBC1D4 interactome in human skeletal muscle