SCA14-Associated PKCγ-G118D Mutant Exhibits a Detrimental Effect on Cerebellar Purkinje Cell Dendritic Growth DOI Open Access
Qin‐Wei Wu, Kejian Wang, Josef P. Kapfhammer

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3688 - 3688

Опубликована: Апрель 14, 2025

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 point mutations or deletions. Among these, spinocerebellar type 14 (SCA14) stems from missense deletions within the PRKCG gene, encoding protein kinase C gamma (PKCγ), pivotal signaling molecule abundant in Purkinje cells. Despite its significance, precise mechanisms underlying how genetic alterations trigger cell malfunction degeneration remain elusive. Given prominent role high expression PKCγ cells, SCA14 presents unique opportunity unravel pathogenesis. A straightforward hypothesis posits that biological activity underlie disease phenotype, there are hints mutated proteins exhibit altered enzymatic Our prior research focused on PKCγ-G118D mutation, commonly found patients, located regulatory domain protein. While cellular assays demonstrated enhanced for PKCγ-G118D, transgenic mice carrying this mutation failed suppressed dendritic development cultures, raising questions about impact living One endogenous might interfere effect PKCγ-G118D. further investigate, we leveraged CRISPR-Cas9 technology generate knockout mouse model integrated it L7-based, cell-specific transfection system analyze effects G118D morphology developing findings reveal that, utilizing approach, exerts detrimental growth, confirming negative influence, indicating potential contribute

Язык: Английский

SCA14-Associated PKCγ-G118D Mutant Exhibits a Detrimental Effect on Cerebellar Purkinje Cell Dendritic Growth DOI Open Access
Qin‐Wei Wu, Kejian Wang, Josef P. Kapfhammer

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3688 - 3688

Опубликована: Апрель 14, 2025

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 point mutations or deletions. Among these, spinocerebellar type 14 (SCA14) stems from missense deletions within the PRKCG gene, encoding protein kinase C gamma (PKCγ), pivotal signaling molecule abundant in Purkinje cells. Despite its significance, precise mechanisms underlying how genetic alterations trigger cell malfunction degeneration remain elusive. Given prominent role high expression PKCγ cells, SCA14 presents unique opportunity unravel pathogenesis. A straightforward hypothesis posits that biological activity underlie disease phenotype, there are hints mutated proteins exhibit altered enzymatic Our prior research focused on PKCγ-G118D mutation, commonly found patients, located regulatory domain protein. While cellular assays demonstrated enhanced for PKCγ-G118D, transgenic mice carrying this mutation failed suppressed dendritic development cultures, raising questions about impact living One endogenous might interfere effect PKCγ-G118D. further investigate, we leveraged CRISPR-Cas9 technology generate knockout mouse model integrated it L7-based, cell-specific transfection system analyze effects G118D morphology developing findings reveal that, utilizing approach, exerts detrimental growth, confirming negative influence, indicating potential contribute

Язык: Английский

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