Inefficient maturation of disease-linked mutant forms of the KCC2 potassium-chloride cotransporter correlates with predicted pathogenicity.

ABSTRACT: The potassium-chloride cotransporter 2 (KCC2) is required for neuronal development, and KCC2 dysregulation is implicated in several neurodevelopmental disorders, including schizophrenia, autism, and epilepsy. A dozen mutations in the KCC2-encoding gene, SLC12A5, are associated with these disorders, but few are fully characterized. To this end, we examined KCC2 biogenesis in a HEK293 cell model. While most of the examined disease-associated mutants matured efficiently, the L403P mutant was unable to traffic to the Golgi. Two other mutants, A191V and R857L, exhibited more subtle defects in maturation. Cell surface biotinylation assays showed that these mutants were also depleted from the cell surface. Another disease-associated variant, R952H, acquired Golgi-associated glycans yet was signif

SUBMITTER: Kok M 

PROVIDER: S-EPMC12001125 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature