PXD038504

PXD038504 is an original dataset announced via ProteomeXchange.

Title	Proinsulin dependent interaction between ENPL-1/GRP94 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.
Description	Maturation of insulin is crucial for insulin secretion and function. ENPL[1]1/GRP94/HSP90B1 plays an important role in this process. ASNA-1/TRC40/GET3 and ENPL-1/GRP94 are conserved insulin secretion regulators in Caenorhabditis elegans and mammals and mouse mutants display type 2 diabetes. ENPL-1 and GRP94 bind proinsulin and regulate proinsulin levels in C. elegans and cultured cells. Here we found that ASNA-1 and ENPL-1 co-operated to regulate insulin secretion in worms via a physical interaction that required pro-DAF-28/insulin but occurred independently of the insulin binding site of ENPL-1. ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The interaction occurred in insulin expressing neurons and was sensitive to changes in pro-DAF-28 levels. The chaperone form of ASNA-1 is likely bound to ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed ASNA[1]1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 which is necessary to maintain proper insulin secretion in C. elegans and provides insights about how their loss might produce diabetes in mammals.
HostingRepository	PRIDE
AnnounceDate	2023-03-10
AnnouncementXML	Submission_2023-03-10_01:01:07.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JohannesFuchs
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-01 16:43:08	ID requested
⏵ 1	2023-03-10 01:01:08	announced

Dataset with its publication pending

submitter keyword: ER chaperone, insulin secretion, diabetes

GautamKao
contact affiliation	Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden
contact email	gautam.kao@gu.se
lab head
JohannesFuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
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/2023/03/PXD038504

PRIDE project URI

• PRIDE
  1. PXD038504
     1. Label: PRIDE project
     2. Name: Proinsulin dependent interaction between ENPL-1/GRP94 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.