PXD006904

PXD006904 is an original dataset announced via ProteomeXchange.

Title	Fc Gamma Receptor (FcγR) Expression and Signaling in the Developing Rat Brain
Description	Maternal antibodies specific for antigens in the developing brain are implicated as risk factors for neurodevelopmental disorders, but how these antibodies interfere with neurodevelopment remain speculative. It has been postulated that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (FcγR) on non-immune cells in the brain, thereby modulating intracellular signaling and/or internalizing function-blocking antibodies specific for intracellular antigens. However, testing this hypothesis has been hindered by the paucity of data regarding FcγR in the developing brain. Thus, we first investigated FcγR expression in the brain of neonatal male and female rats using quantitative PCR analyses. FcgrIa, FcgrIIa, FcgrIIb, FcgrIIIa and Fcgrt transcripts were detectable in the cortex, hippocampus and cerebellum at postnatal days 1 and 7. These transcripts were also present in primary hippocampal and cortical cell cultures, where their expression was upregulated by IFNγ. In order to confirm protein abundance of FcγRIa, FcγRIIb and FcγRIIIa in cultured hippocampal and cortical neurons and astrocytes on the single cell and tissue level we used immunocytochemistry, western blotting, proteotype analysis, and flow cytometry. The data shows that a subpopulation of these cells co-express the excitatory FcγRIa and the inhibitory FcγRIIb. Functional analysis shows that exposure of hippocampal and cortical cell cultures to IgG-IC increased intracellular calcium and Erk phosphorylation, and triggered FcγR-mediated internalization of IgG. Collectively, these data demonstrate that developing neurons and astrocytes express signaling competent FcγR. which could establish a molecular mode of action of maternal antibodies could influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain. These findings support the hypothesis that maternal antibodies influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain.
HostingRepository	PRIDE
AnnounceDate	2018-01-11
AnnouncementXML	Submission_2018-01-11_02:35:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marc van Oostrum
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-10 00:42:52	ID requested
⏵ 1	2018-01-11 02:35:04	announced

Stamou M, Grodzki AC, van Oostrum M, Wollscheid B, Lein PJ, Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. J Neuroinflammation, 15(1):7(2018) [pubmed]

curator keyword: Biological

submitter keyword: Brain, neuron culture, Fc gamma receptors

Bernd Wollscheid
contact affiliation	Department of Health Sciences and Technology (D-HEST) Institute of Molecular Systems Biology (IMSB) ETH Zürich
contact email	wbernd@ethz.ch
lab head
Marc van Oostrum
contact affiliation	ETH Zürich
contact email	marcv@ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006904
     1. Label: PRIDE project
     2. Name: Fc Gamma Receptor (FcγR) Expression and Signaling in the Developing Rat Brain