Characterization of the disease-causing mechanism of KIF3B mutations from ciliopathy patients.

ABSTRACT: The heterodimeric kinesin-2 motor (KIF3A/KIF3B with accessory protein KAP3) drives intraflagellar transport, essential for ciliogenesis and ciliary function. Three point mutations in the KIF3B subunit have recently been linked to disease in humans (E250Q and L523P) and Bengal cats (A334T) (Cogné et al., Am. J. Hum. Genet., 2020, 106, 893-904). Patients display retinal atrophy and, in some cases, other ciliopathy phenotypes. However, the molecular mechanism leading to disease is currently unknown. Here, we used Kif3a ^-/- ;Kif3b ^-/- (knockout) 3T3 cells, which cannot make cilia, to characterize these mutations. While reexpression of KIF3B(E250Q) and KIF3B(L523P) did not rescue ciliogenesis, reexpression of wildtype or KIF3B(A334T) restored ciliogene

SUBMITTER: Adams JM 

PROVIDER: S-EPMC11043552 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature