PXD053259-1

PXD053259 is an original dataset announced via ProteomeXchange.

Title	Loss of epilepsy-associated CDKL5 kinase alters synaptic signaling pathways throughout development
Description	Lesions of the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are associated with a severe developmental epileptic encephalopathy called CDKL5 deficiency disorder (CDD). CDKL5 is a serine-threonine kinase that has been implicated as a regulator of synaptic functioning, and its loss results in multiple behavioral phenotypes in animal models, including hippocampus-dependent learning and memory deficits. To determine how the loss of CDKL5 alters biochemical signaling pathways at the synapse and in the hippocampus in vivo, we isolated cortical synaptosomes and whole hippocampal tissue from CDD mice for proteomic and phosphoproteomic analysis. Furthermore, CDKL5 is known to have important developmental and post-developmental roles in the brain, so we collected tissues at both early postnatal and later adolescent timepoints to elucidate how signaling pathway alterations differ across development. Our DIA-based mass spectrometry results revealed that loss of CDKL5 alters multiple synaptic and hippocampal signaling pathways, with changes predominantly reflecting altered protein phosphorylation status, not changes in protein abundance. Differently regulated proteins were enriched for multiple synaptic and neuronal signaling pathways during and after early development, with a couple of notable examples including altered phosphorylation of proteins important for the synaptic vesicle cycle and Rho GTPase signaling. Overall, our findings highlight several biochemical signaling pathways that are altered in CDD and informs future mechanistic and therapeutic studies aiming to better understand and treat CDD.
HostingRepository	jPOST
AnnounceDate	2024-06-20
AnnouncementXML	Submission_2024-06-20_13:06:06.491.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marco Hadisurya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide; O-phospho-L-serine; O-phospho-L-threonine; O4'-phospho-L-tyrosine
Instrument	instrument

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-20 13:04:49	ID requested
⏵ 1	2024-06-20 13:06:06	announced

Dataset with its publication pending

submitter keyword: CDKL5 deficiency disorder, CDD, proteomics, phosphoproteomics, DIA mass spectrometry, synaptosomes

W. Andy Tao, Zhaolan Zhou
lab head
Marco Hadisurya
contact affiliation	Purdue University
dataset submitter

jPOST dataset URI

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