LIMK1 variants are associated with divergent endocrinological phenotypes and altered exocytosis dynamics.

ABSTRACT: LIM kinase 1 (LIMK1) plays a pivotal role in dynamic actin remodeling through phosphorylation of cofilin, thereby regulating exocytosis. We report two individuals harboring LIMK1 de novo variants with dissimilar phenotypes: one exhibited epileptic encephalopathy and developmental delay, while the other showed common variable immune deficiency and glucose dysregulation. We suspected that the divergent phenotypic features arose from opposing effects on LIMK1 activity. Indeed, actin polymerization was significantly decreased in individual 1, whereas it was increased in individual 2. Insulin-secreting cell lines expressing the LIMK1 variant of individual 1 exhibited significantly slower exocytosis, contrasting the rapid and uncontrolled exocytosis in individual 2. Intriguingly, b

SUBMITTER: Muffels IJJ 

PROVIDER: S-EPMC12146536 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature