title: Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking.
abstract: Sensory cilia are populated by a select group of signaling proteins that detect environmental stimuli. How these molecules are delivered to the sensory cilium and whether they rely on one another for specific transport remains poorly understood. Here, we investigated whether the visual pigment, rhodopsin, is critical for delivering other signaling proteins to the sensory cilium of photoreceptor cells, the outer segment. Rhodopsin is the most abundant outer segment protein and its proper transport is essential for formation of this organelle, suggesting that such a dependency might exist. Indeed, we demonstrated that guanylate cyclase-1, producing the cGMP second messenger in photoreceptors, requires rhodopsin for intracellular stability and outer segment delivery. We elucidated this dependency by showing that guanylate cyclase-1 is a novel rhodopsin-binding protein. These findings expand rhodopsin's role in vision from being a visual pigment and major outer segment building block to directing trafficking of another key signaling protein.
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, United States.
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Pearring
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, United States.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United States.
authors.forename: William J
authors.initials: WJ
authors.lastname: Spencer
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, United States.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lieu
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, United States.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United States.
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Arshavsky
mesh_terms: D000818:Animals; D006162:Guanylate Cyclase / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010786:Photoreceptor Cells / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012243:Rhodopsin / Q000172:deficiency / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D012243:Rhodopsin; D006162:Guanylate Cyclase
keywords: guanylate cyclase; membrane protein trafficking; mouse; neuroscience; photoreceptor; rhodopsin; sensory cilium