PXD028142 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | KCNQ2 and KCNQ5 can form a channel complex in the brain independent of KCNQ3 channels |
Description | KCNQ2 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-24 |
AnnouncementXML | Submission_2022-03-24_12:28:54.348.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jeremy Balsbaugh |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-08-26 04:05:54 | ID requested | |
⏵ 1 | 2022-03-24 12:28:55 | announced | |
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 affiliation | Proteomics & Metabolomics Facility, University of Connecticut |
contact email | jeremy.balsbaugh@uconn.edu |
lab head | |
Jeremy Balsbaugh |
contact affiliation | University of Connecticut |
contact email | jeremy.balsbaugh@uconn.edu |
dataset submitter | |
Full Dataset Link List
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/2022/03/PXD028142 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028142
- Label: PRIDE project
- Name: KCNQ2 and KCNQ5 can form a channel complex in the brain independent of KCNQ3 channels