Light Regulates the Ciliary Protein Transport and Outer Segment Disc Renewal of Mammalian Photoreceptors

•Light regulates the rod OS entry of rhodopsin•PRPH2 enters the OS following a rhythm complementary to that of rhodopsin•Rod OS discs formed during the day and night have distinct composition and morphology•Cyclic light governs the periodicity of the OS disc arrangement and cytostructure

SummaryThe outer segment (OS) of the rod photoreceptor is a light-sensing cilium containing ∼1,000 membrane-bound discs. Each day, discs constituting the distal tenth of the OS are shed, whereas nascent discs are formed at the base of the OS through the incorporation of molecules transported from the inner segment. The mechanisms regulating these processes remain elusive. Here, we show that rhodopsin preferentially enters the OS in the dark. Photoexcitation of post-Golgi rhodopsins retains them in the inner segment. Disc-rim protein peripherin2/rds enters the OS following a rhythm complementary to that of rhodopsin. Light-dark cycle-regulated protein trafficking serves as a mechanism to segregate rhodopsin-rich and peripherin2/rds-rich discs into alternating stacks, which are flanked by characteristic cytoplasmic pockets. This periodic cytostructure divides the OS into approximately ten fractions, each containing discs synthesized in a single day. This mechanism may explain how the rod photoreceptor balances the quantity of discs added and removed daily.