PXD052896-1

PXD052896 is an original dataset announced via ProteomeXchange.

Title	Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology
Description	The Ras-related Rap1A GTPase is implicated in pancreas β-cell insulin secretion, and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study we examined the differential proteomic profiles by nanoLC-ESI-MS/MS of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice, to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreas. Functional enrichment analysis showed 4 of the 8 Null unique proteins, ERO1-like protein β (Ero1lβ), triosephosphate isomerase (TP1), 14-3-3 protein γ and kallikrein-1, were exclusively involved in insulin biogenesis, with role in insulin metabolism. Specifically, the mRNA expression of Ero1lβ and TP1 was significantly (p<0.05) increased in Null versus WT pancreas. Rap1A-deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge, but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised as compared to WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_05:27:44.609.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Durrey Shahwar
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-06 04:24:29	ID requested
⏵ 1	2024-10-17 05:27:45	announced

10.3390/ijms25158013;

Shahwar D, Baqai S, Khan F, Khan MI, Javaid S, Hameed A, Raza A, Saleem Uddin S, Hazrat H, Rahman MH, Musharraf SG, Chotani MA, Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology. Int J Mol Sci, 25(15):(2024) [pubmed]

submitter keyword: oral glucose tolerance test

insulin tolerance test, glucose-stimulated insulin secretion,Pancreas

Intracellular signaling

Rap1A-GTPase

Gene knockout

Differential expression

nanoLC-ESIMS/MS

Ero1lβ expression

Dr. Maqsood Ahmed Chotani
contact affiliation	Molecular Signaling Laboratory, Dr. Panjwani Center forMolecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
contact email	maqsood.chotani@gmail.com
lab head
Durrey Shahwar
contact affiliation	University of Karachi
contact email	shahwarshahshahwar@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052896
     1. Label: PRIDE project
     2. Name: Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology