PXD041769

PXD041769 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic analysis of Ank2-mutant mice
Description	Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:09.629.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yeji Yang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-24 04:05:06	ID requested
1	2023-07-20 11:14:08	announced
⏵ 2	2023-11-14 09:03:13	announced	2023-11-14: Updated project metadata.

Oh H, Lee S, Oh Y, Kim S, Kim YS, Yang Y, Choi W, Yoo YE, Cho H, Lee S, Yang E, Koh W, Won W, Kim R, Lee CJ, Kim H, Kang H, Kim JY, Ku T, Paik SB, Kim E, Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice. Nat Commun, 14(1):3547(2023) [pubmed]

submitter keyword: Autism spectrum disorders, Phosphoproteomics, Ank2, LC-MS/MS

Eunjoon Kim
contact affiliation	Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Korea
contact email	kime@kaist.ac.kr
lab head
Yeji Yang
contact affiliation	Korea Basic Science Institute
contact email	yangyj@kbsi.re.kr
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/PXD041769

PRIDE project URI

• PRIDE
  1. PXD041769
     1. Label: PRIDE project
     2. Name: Phosphoproteomic analysis of Ank2-mutant mice