PXD047434

PXD047434 is an original dataset announced via ProteomeXchange.

Title	IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport
Description	Mutations in the IER3IP1 (Immediate early response-3 interacting protein 1) gene can cause MEDS1 (microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome-1), a severe disease leading to death in early childhood. The small endoplasmic reticulum-membrane protein IER3IP1 has a non-essential role in ER-Golgi transport. We here use secretome and cell-surface proteomics to show that the loss of IER3IP1 or expression of the pathogenic p.L78P-mutation causes ER retention of selective cell-surface receptors and secreted proteins involved in neuronal migration. This correlates with distension of ER membranes and increased lysosomal activity. Trafficking of the cargo receptor ERGIC53 and of KDEL-receptor 2 are impaired, the latter causing the aberrant secretion of ER-localized chaperones. In utero knock-down of IER3IP1 in brains of mouse embryos displays a morphological phenotype of newborn neurons. Taken together, our data provide hints on how the loss or mutation of a 10 kDa small ER-membrane protein can cause a fatal syndrome.
HostingRepository	MassIVE
AnnounceDate	2024-08-08
AnnouncementXML	Submission_2024-08-08_05:58:08.177.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Leibniz FLI Proteomics
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-01 01:34:03	ID requested
⏵ 1	2024-08-08 05:58:08	announced

no publication

submitter keyword: endoplasmic reticulum, COPII, anterograde transport, microcephaly, diabetes, axon pathfinding, cortical development

Christoph Kaether
contact affiliation	Leibniz Institute on Aging, Fritz Lipmann Institute (FLI)
contact email	Christoph.Kaether@leibniz-fli.de
lab head
Leibniz FLI Proteomics
contact affiliation	Leibniz FLI
contact email	proteomics@leibniz-fli.de
dataset submitter

MassIVE dataset URI

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://massive.ucsd.edu/v06/MSV000093547/