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PXD028142

PXD028142 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKCNQ2 and KCNQ5 can form a channel complex in the brain independent of KCNQ3 channels
DescriptionKCNQ2 and KCNQ3 channels are associated with multiple neurodevelopmental disorders and are also therapeutic targets for neurological and neuropsychiatric diseases. The current dogma is that, in the brain, KCNQ2 forms diheteromeric channels with KCNQ3, but not with KCNQ5, a channel also resident in neurons. Here, we investigated whether KCNQ2 channels can form functional triheteromeric channels with KCNQ3 and KCNQ5. We applied split-intein-mediated protein trans-splicing to form KCNQ2-KCNQ5 diheteromeric channels followed by co-expression with KCNQ3 to form triheterometic channels. Unexpectedly, we found that KCNQ2-KCNQ5 tandems can form functional channels that are regulated by KCNQ3 and PIP2 levels. Using an epitope-tagged Kcnq2 mouse and mass spectrometry, we also demonstrated that KCNQ2 channels can associate with KCNQ5 channels in the absence of KCNQ3 channels in the brain. Thus, KCNQ2 channel composition is much more diverse than has been previously recognized, necessitating a re-examination of the genotype–phenotype relationship of KCNQ2 pathogenic variants.
HostingRepositoryPRIDE
AnnounceDate2022-03-24
AnnouncementXMLSubmission_2022-03-24_12:28:54.348.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeremy Balsbaugh
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-26 04:05:54ID requested
12022-03-24 12:28:55announced
Publication List
Soh H, Springer K, Doci K, Balsbaugh JL, Tzingounis AV, KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3. Proc Natl Acad Sci U S A, 119(13):e2117640119(2022) [pubmed]
Keyword List
submitter keyword: KCNQ2, KCNQ3, KCNQ5, epilepsy, neurodevelopmental disorders, channelopathy, autism spectrum disorders, co-immunoprecipitation, mass spectrometry
Contact List
Jeremy Balsbaugh
contact affiliationProteomics & Metabolomics Facility, University of Connecticut
contact emailjeremy.balsbaugh@uconn.edu
lab head
Jeremy Balsbaugh
contact affiliationUniversity of Connecticut
contact emailjeremy.balsbaugh@uconn.edu
dataset submitter
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Dataset FTP location
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