FBXO41

Cilia effects upon perturbation of FBXO41

Overexpression effect:

Shorter cilia

Phenotypes

Mouse phenotype:

hyperactivity; decreased grip strength; decreased circulating cholesterol level; increased startle reflex

Mouse ciliopathy phenotype:

increased kidney weight; eye hemorrhage; abnormal auditory brainstem response

Subcellular localization

basal body

Functional category

• Signaling (Hedgehog, GPCRs, ion channels)
• Ciliary assembly/disassembly
• Cilia???cytoskeleton/adhesion links

Function

Fbxo41 as a novel Skp1/Cullin1/F-box (SCF) E3-ligase complex subunit that targets to neuronal centrioles where its accumulation promotes disassembly of primary cilia, and affects sonic hedgehog signaling, a canonical ciliary pathway. Fbxo41 targeting to centrioles requires its Coiled-coil and F-box domains. Levels of Fbxo41 at the centrioles inversely correlate with neuronal cilia length, and mutations that disrupt Fbxo41 targeting or assembly into SCF-complexes also disturb its function in cilia disassembly and signaling. Fbxo41 dependent cilia disassembly in mitotic and post-mitotic cells requires rearrangements of the actin-cytoskeleton, but requires Aurora A kinase activation only in mitotic cells, highlighting important mechanistical differences controlling cilia size between mitotic and post-mitotic cells(31160656).