PXD032712

PXD032712 is an original dataset announced via ProteomeXchange.

Title	Patient-derived recombinant autoantibodies reveal the subcellular neuroglial distribution and heterogeneous interactome of leucine-rich glioma-inactivated 1
Description	Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localisation of these features, and gain broader insights into LGI1’s neurobiology, we analysed the detailed distribution of LGI1, and the diversity of its protein interactome, in mouse brains using recombinant monoclonal LGI1-antibodies derived from encephalitis patients. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neuro-oligodendrocytic and astro-microglial protein complexes. Proteomic data support the hypothesis that destabilization of Kv1 / MAGUK complexes by autoantibodies could promote excitability, but did not reveal LGI1 complexes with postsynaptic glutamate receptors. Our results extend our understanding of regional, cellular and subcellular LGI1 expression profiles and reveal novel LGI1-associated complexes, thus providing insights into the complex biology of LGI1 and its relationship to seizures and memory loss.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:05:27.240.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maya BELGHAZI
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-23 02:50:59	ID requested
1	2023-07-10 06:23:32	announced
⏵ 2	2023-11-14 07:05:27	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Auto-antibodies, Limbic Encephalitis, Autosomal-dominant lateral temporal lobe epilepsy (ADLTE), Kv1 channels,Leucin-rich Glioma inactivated 1 (LGI1), ADAM

Oussama EL FAR
contact affiliation	Inserm UNIS UMR_S 1072 51 Boulevard Pierre Dramard 13015 Marseille FRANCE
contact email	oussama.el-far@univ-amu.fr
lab head
Maya BELGHAZI
contact affiliation	CNRS
contact email	maya.belghazi@univ-amu.fr
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/2023/07/PXD032712

PRIDE project URI

• PRIDE
  1. PXD032712
     1. Label: PRIDE project
     2. Name: Patient-derived recombinant autoantibodies reveal the subcellular neuroglial distribution and heterogeneous interactome of leucine-rich glioma-inactivated 1