The Kelch 3 motif on gigaxonin mediates the interaction with NUDCD3 and regulates vimentin filament morphology.

ABSTRACT: Gigaxonin is an intermediate filament (IF)-interacting partner belonging to the Kelch-like (KLHL) protein family. Gigaxonin is encoded by the KLHL16 gene, which is mutated in Giant Axonal Neuropathy (GAN). The lack of functional gigaxonin in GAN patient cells impairs IF proteostasis by affecting IF protein degradation and transport. This leads to focal abnormal accumulations of IFs and compromised cellular function, with neurons being most severely impacted. We hypothesized that gigaxonin forms molecular interactions via specific sequence motifs to regulate IF proteostasis. The goal of this study was to examine how distinct Kelch motifs on gigaxonin regulate IF protein degradation and filament morphology. We analyzed vimentin IFs in HEK293 cells overexpressing wild type (WT) gigaxonin, or

SUBMITTER: Phillips CL 

PROVIDER: S-EPMC12403043 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature