{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:00:01Z","timestamp":1760162401072,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anhui Provincial Natural Science Foundation","award":["2408085QH277","2024AH050075","310030_189083"],"award-info":[{"award-number":["2408085QH277","2024AH050075","310030_189083"]}]},{"name":"Natural Science Research Project of Anhui Educational Committee","award":["2408085QH277","2024AH050075","310030_189083"],"award-info":[{"award-number":["2408085QH277","2024AH050075","310030_189083"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["2408085QH277","2024AH050075","310030_189083"],"award-info":[{"award-number":["2408085QH277","2024AH050075","310030_189083"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Scholarship Fund of China Scholarship Council, Ministry of Education of the People\u2019s Republic of China","award":["2408085QH277","2024AH050075","310030_189083"],"award-info":[{"award-number":["2408085QH277","2024AH050075","310030_189083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinocerebellar ataxia (SCA), an autosomal dominant neurodegenerative condition, is marked by a gradual deterioration of cerebellar function. To date, more than 40 distinct SCA subtypes have been identified, with some attributed to CAG repeat expansions and others to point mutations or deletions. Among these, spinocerebellar ataxia type 14 (SCA14) stems from missense mutations or deletions within the PRKCG gene, encoding protein kinase C gamma (PKC\u03b3), a pivotal signaling molecule abundant in Purkinje cells. Despite its significance, the precise mechanisms underlying how genetic alterations trigger Purkinje cell malfunction and degeneration remain elusive. Given the prominent role and high expression of PKC\u03b3 in Purkinje cells, SCA14 presents a unique opportunity to unravel the underlying pathogenesis. A straightforward hypothesis posits that alterations in the biological activity of PKC\u03b3 underlie the disease phenotype, and there are hints that mutated PKC\u03b3 proteins exhibit altered enzymatic function. Our prior research focused on the PKC\u03b3-G118D mutation, commonly found in SCA14 patients, located in the regulatory domain of the protein. While cellular assays demonstrated enhanced enzymatic activity for PKC\u03b3-G118D, transgenic mice carrying this mutation failed to exhibit suppressed dendritic development in cerebellar cultures, raising questions about its impact within living Purkinje cells. One hypothesis is that endogenous PKC\u03b3 might interfere with the expression or effect of PKC\u03b3-G118D. To further investigate, we leveraged CRISPR-Cas9 technology to generate a PKC\u03b3 knockout mouse model and integrated it with an L7-based, Purkinje cell-specific transfection system to analyze the effects of G118D protein expression on the dendritic morphology of developing Purkinje cells. Our findings reveal that, utilizing this approach, PKC\u03b3-G118D exerts a detrimental effect on Purkinje cell growth, confirming its negative influence, indicating that the potential of the G118D mutation to contribute to SCA14 pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms26083688","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:18:36Z","timestamp":1744611516000},"page":"3688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SCA14-Associated PKC\u03b3-G118D Mutant Exhibits a Detrimental Effect on Cerebellar Purkinje Cell Dendritic Growth"],"prefix":"10.3390","volume":"26","author":[{"given":"Qin-Wei","family":"Wu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Anhui University, Hefei 230601, China"},{"name":"Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kejian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anhui University, Hefei 230601, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-5778","authenticated-orcid":false,"given":"Josef P.","family":"Kapfhammer","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Department of Biomedicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuron.2023.01.021","article-title":"Diverse Regional Mechanisms Drive Spinocerebellar Ataxia Type 1 Phenotypes","volume":"111","author":"Putka","year":"2023","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-neuro-100423-104943","article-title":"V Cerebellar Functions Beyond Movement and Learning","volume":"47","author":"Kim","year":"2024","journal-title":"Annu. 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