INF2 formin variants linked to human inherited kidney disease reprogram the transcriptome, causing mitotic chaos and cell death.

ABSTRACT: Mutations in the human INF2 gene cause autosomal dominant focal segmental glomerulosclerosis (FSGS)-a condition characterized by podocyte loss, scarring, and subsequent kidney degeneration. To understand INF2-linked pathogenicity, we examined the effect of pathogenic INF2 on renal epithelial cell lines and human primary podocytes. Our study revealed an increased incidence of mitotic cells with surplus microtubule-organizing centers fostering multipolar spindle assembly, leading to nuclear abnormalities, particularly multi-micronucleation. The levels of expression of exogenous pathogenic INF2 were similar to those of endogenous INF2. The aberrant nuclear phenotypes were observed regardless of the expression method used (retrovirus infection or plasmid transfection) or the promoter (LTR or C

SUBMITTER: Labat-de-Hoz L 

PROVIDER: S-EPMC11335204 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature