The tectonic complex regulates membrane protein composition in the photoreceptor cilium
Truong HM, Cruz-Colón KO, Martínez-Márquez JY, Willer JR, Travis AM, Biswas SK, Lo WK, Bolz HJ, Pearring JN
Stop-motion film showing our proposed model depicting tectonic’s role in photoreceptors to prevent non-ciliary membrane proteins from infiltrating into the ciliary outer segment compartment. In the absence of the tectonic complex, we did not observe structural defects in the transition zone or ciliary transport carriers, but increased diffusion through the transition zone leads to non-ciliary membrane proteins, such as Stx3, becoming enriched in the enclosed membrane discs of the outer segment over time.
Aberrant Arl3 activity drives nuclear migration defect in rod photoreceptors
Travis AM, Manocha S, Willer JR, Wessler TS, Skiba NP, Pearring JN
The small GTPase Arl3 is important for the enrichment of lipidated proteins to primary cilia, including the outer segment of photoreceptors. Human mutations ARL3 cause both autosomal recessive and dominant inherited retinal dystrophies. We discovered that dominant mutations result in increased active G-protein—Arl3-D67V has constitutive activity and Arl3-Y90C is fast cycling—and their expression in mouse rods resulted in a displaced nuclear phenotype due to an aberrant Arl3-GTP gradient. We go on to show that removing or restoring the Arl3-GTP gradient within the cilium is sufficient to rescue the nuclear migration defect. Our results reveal that an Arl3 ciliary gradient is involved in proper positioning of photoreceptor nuclei during retinal development.