PXD028142

PXD028142 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-26 04:05:54	ID requested
⏵ 1	2022-03-24 12:28:55	announced

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]

submitter keyword: KCNQ2, KCNQ3, KCNQ5, epilepsy, neurodevelopmental disorders, channelopathy, autism spectrum disorders, co-immunoprecipitation, mass spectrometry

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

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

• PRIDE
  1. PXD028142
     1. Label: PRIDE project
     2. Name: KCNQ2 and KCNQ5 can form a channel complex in the brain independent of KCNQ3 channels