PXD028096

PXD028096 is an original dataset announced via ProteomeXchange.

Title	The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system
Description	Proteolytic ectodomain shedding of membrane proteins is a fundamental mechanism to control the communication between cells and their environment. A key protease for membrane protein shedding is ADAM17, which requires a non-proteolytic subunit, either inactive Rhomboid 1 (iRhom1) or iRhom2 for its activity. While iRhom1 and iRhom2 are coexpressed in most tissues and appear to have largely redundant functions, the brain is an organ with predominant expression of iRhom1. Yet, little is known about the spatio-temporal expression of iRhom1 in mammalian brain and about its function in controlling membrane protein shedding in the nervous system. Here, we demonstrate that iRhom1 is expressed in mouse brain from the prenatal stage to adulthood with a peak in early postnatal development. In the adult mouse brain iRhom1 was widely expressed, including in cortex, hippocampus, olfactory bulb and cerebellum. Proteomic analysis of the secretome of primary neurons and of cerebrospinal fluid (CSF), obtained from iRhom1-deficient and control mice, identified several membrane proteins that require iRhom1 for their shedding in vitro or in vivo. One of these proteins was the ‘multiple-EGF-like-domains protein 10’ (MEGF10), a phagocytic receptor in the brain that is linked to the removal of amyloid  and apoptotic neurons. MEGF10 was further validated as an ADAM17 substrate using ADAM17-deficient mouse embryonic fibroblasts. Taken together, this study discovers a role for iRhom1 in controlling membrane protein shedding in the mouse brain, establishes MEGF10 as an iRhom1-dependent ADAM17 substrate and demonstrates that iRhom1 is widely expressed in murine brain.
HostingRepository	PRIDE
AnnounceDate	2021-10-07
AnnouncementXML	Submission_2021-10-07_02:32:18.732.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-24 07:07:03	ID requested
⏵ 1	2021-10-07 02:32:19	announced

T, ü, shaus J, M, ü, ller SA, Shrouder J, Arends M, Simons M, Plesnila N, Blobel CP, Lichtenthaler SF, The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system. FASEB J, 35(11):e21962(2021) [pubmed]

submitter keyword: Mouse, Neuron, CSF, hiSPECS

Stefan F. Lichtenthaler
contact affiliation	DZNE Munich Neuroproteomics Feodor-Lynen Str. 17 81377 Munich Germany
contact email	stfan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028096
     1. Label: PRIDE project
     2. Name: The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system