title: The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors.
abstract: Retinal guanylate cyclases 1 and 2 (GC1 and GC2) are responsible for synthesis of cyclic GMP in rods and cones, but their individual contributions to phototransduction are unknown. We report here that the deletion of both GC1 and GC2 rendered rod and cone photoreceptors nonfunctional and unstable. In the rod outer segments of GC double knock-out mice, guanylate cyclase-activating proteins 1 and 2, and cyclic GMP phosphodiesterase were undetectable, although rhodopsin and transducin alpha-subunit were mostly unaffected. Outer segment membranes of GC1-/- and GC double knock-out cones were destabilized and devoid of cone transducin (alpha- and gamma-subunits), cone phosphodiesterase, and G protein-coupled receptor kinase 1, whereas cone pigments were present at reduced levels. Real time reverse transcription-PCR analyses demonstrated normal RNA transcript levels for the down-regulated proteins, indicating that down-regulation is posttranslational. We interpret these results to demonstrate an intrinsic requirement of GCs for stability and/or transport of a set of membrane-associated phototransduction proteins.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah 84112, USA. wbaehr@hsc.utah.edu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
authors.forename: Sukanya
authors.initials: S
authors.lastname: Karan
authors.forename: Tadao
authors.initials: T
authors.lastname: Maeda
authors.forename: Dong-Gen
authors.initials: DG
authors.lastname: Luo
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: J Darin
authors.initials: JD
authors.lastname: Bronson
authors.forename: Carl B
authors.initials: CB
authors.lastname: Watt
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Frederick
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004596:Electroretinography / Q000379:methods; D017353:Gene Deletion; D006162:Guanylate Cyclase / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012374:Rod Cell Outer Segment
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase; C484780:Gucy2e protein, mouse; C484783:Gucy2f protein, mouse