{"database":"JPOST Repository","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["https://storage.jpostdb.org/JPST004393/files/Hippocampus_34_Fractions_Phospho_Library.kit","https://storage.jpostdb.org/JPST004393/files/Hippocampus_6Week_DIA_Phosphoproteomics_16%20samples.zip","https://storage.jpostdb.org/JPST004393/files/Hippocampus_2Week_DIA_Phosphoproteomics_16%20samples.zip","https://storage.jpostdb.org/JPST004393/files/Hippocampus_2_Week_Phosphoproteome.sne","https://storage.jpostdb.org/JPST004393/files/Hippocampus_Proteome_directDIA.sne","https://storage.jpostdb.org/JPST004393/files/Hippocampus_Proteome.zip","https://storage.jpostdb.org/JPST004393/files/DDA_Library_Hippocampus_20fractions.zip","https://storage.jpostdb.org/JPST004393/files/Hippocampus_6_Week_Phosphoproteome.sne"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["W. Andy Tao, Zhaolan Zhou"],"species":["Mus Musculus (mouse)"],"full_dataset_link":["https://repository.jpostdb.org/entry/JPST004393"],"submitter_affiliation":["Purdue University"],"sample_protocol":[""],"repository":["jPOST"],"data_protocol":[""],"additional_accession":[]},"is_claimable":false,"name":"Phosphoproteomic characterization of altered signaling pathways across hippocampus development upon loss of epilepsy-associated CDKL5 kinase ","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 neuronal functioning, and its loss results in multiple behavioral phenotypes in animal models. One example, hippocampus-dependent learning and memory deficits, represents a clinically relevant phenotype that is reproducible across studies. To determine how losing CDKL5 alters biochemical signaling pathways in the hippocampus in vivo, we isolated whole hippocampal tissue from CDD mice for proteomic and phosphoproteomic analysis. Furthermore, CDKL5 is known to have important early 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 biochemical signaling pathways, with changes predominantly reflecting altered protein phosphorylation, not changes in protein abundance. Differently regulated proteins were enriched for multiple synaptic and cytoskeletal signaling pathways during and after early development. 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. ","dates":{"publication":"Mon Apr 27 00:00:00 BST 2026"},"accession":"PXD074369","cross_references":{"TAXONOMY":["10090"]}}