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PXD019109

PXD019109 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSoluble SORLA enhances neurite outgrowth and regeneration through activation of EGFR and MAPK pathways
DescriptionSORLA is a type I transmembrane component associated with Alzheimers disease (AD) risk. Although SORLA is abundantly expressed in neurons, physiological roles for SORLA remain yet unclear. Here, we show that cultured neurons overexpressing SORLA (SORLA TG) feature enhanced neurite length, and accelerated neurite regeneration with wounding. Enhanced accumulation of a soluble SORLA form (sSORLA) is observed in SORLA TG neurons, where purified sSORLA can sufficiently drive neurite extension and regeneration. Phosphoproteomic analysis indicates enrichment of phosphoproteins related to the EGFR/ERK pathway in SORLA TG hippocampus. We find that sSORLA can co-precipitate with EGFR in vitro, where sSORLA treatment can induce EGFR Y1173 phosphorylation in cultured neurons. sSORLA also triggers Erk activation and downstream c-fos upregulation/nuclear translocation, where pharmacological EGFR or ERK inhibition reversed enhancements in sSORLA-dependent neurite regeneration. Together, these results implicate the EGFR as a sSORLA receptor which activates ERK/c-Fos pathways to enhance neurite extension, outgrowth and regeneration.
HostingRepositoryMassIVE
AnnounceDate2020-09-09
AnnouncementXMLSubmission_2020-09-09_16:14:18.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlexandre Rosa Campos
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListPhospho
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-12 00:40:04ID requested
12020-09-09 16:14:18announced
Publication List
no publication
Keyword List
submitter keyword: Alzheimers disease, SORLA
Contact List
Timothy Y. Huang
contact affiliationSanford Burnham Prebys Medical Discovery Institute
contact emailthuang@sbpdiscovery.org
lab head
Alexandre Rosa Campos
contact affiliationSBP Medical Discovery Institute
contact emailarosacampos@sbpdiscovery.org
dataset submitter
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MassIVE dataset URI
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