Gene

Cell biology

Cilium

Neuroscience

Biology

Retina

Lamellipodium

Retinal

Axoneme

Biochemistry

Genetics

Actin

Anatomy

Flagellum

Cytoskeleton

Rhodopsin

Cell

Colocalization

Visual phototransduction

Opsin

Proceedings of the National Academy of Sciences

Significance The photoreceptor outer segments are primary cilia, modified for phototransduction by incorporation of stacked opsin-loaded membrane disks that are continuously regenerated. This process is disrupted in several types of inherited retinal dystrophy, but the driving force remained unclear. We show that C2orf71/PCARE (photoreceptor cilium actin regulator), associated with inherited retinal dystrophy subtype RP54, efficiently recruits the Arp2/3 complex activator WASF3 to the cilium. This activates an actin dynamics-driven expansion of the ciliary tip, resembling membrane evagination in lamellipodia formation. Colocalization of this actin dynamics module to the base of the outer segments, and absence thereof in Pcare −/− mice, suggests PCARE-regulated actin dynamics as a critical process in outer segment disk formation.

PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation