PXD047434-1

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

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