PXD060630-1

PXD060630 is an original dataset announced via ProteomeXchange.

Title	Sex specific disruptions in PKCγ signaling in a mouse model of Spinocerebellar Ataxia Type 14
Description	Spinocerebellar Ataxia Type 14 (SCA14) is an autosomal dominant neurodegenerative disease caused by mutations in the gene-encoding protein kinase C gamma (PKCγ), a Ca2+/diacylglycerol (DG)-dependent serine/threonine kinase dominantly expressed in the Purkinje cells of the cerebellum, a brain region that regulates motor function. These mutations impair autoinhibitory constraints to increase the basal activity of the kinase, resulting in dysregulated cerebellar function. To better understand the phenotypic impact of aberrant PKCγ signaling in disease pathology, we developed a knock-in murine model of the SCA14 mutation ΔF48 in PKCγ. This fully penetrant mutation is one of the most severe in humans, with the age of disease onset in early childhood. Genetic, behavioral, and molecular testing revealed that ΔF48 PKCγ SCA14 mice have sex-specific, ataxia related phenotypes, and that ΔF48 PKCγ distinctly alters the cerebellar phosphoproteome in SCA14 male and female mice. Analysis of existing human data reveal that SCA14 has a significantly earlier age of onset for males compared with females. Our data reveal that sex-specific differences in SCA14 pathology arise from the clinically relevant ΔF48 PKCγ mutation and suggest that treatment strategies to modulate aberrant PKCγ may be particularly beneficial in males.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_16:09:00.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-10 08:10:21	ID requested
⏵ 1	2026-03-16 16:09:00	announced

Dataset with its publication pending

submitter keyword: phosphoproteome,Mouse, PKC, phosphorylation

Alexandra C. Newton1
contact affiliation	Department of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA.
contact email	anewton@health.ucsd.edu
lab head
Majid Ghassemian
contact affiliation	Scientist
contact email	mghassem@ucsd.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060630
     1. Label: PRIDE project
     2. Name: Sex specific disruptions in PKCγ signaling in a mouse model of Spinocerebellar Ataxia Type 14