The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors.
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.
Baehr
Wolfgang
W
Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah 84112, USA. wbaehr@hsc.utah.edu
Karan
Sukanya
S
Maeda
Tadao
T
Luo
Dong-Gen
DG
Li
Sha
S
Bronson
J Darin
JD
Watt
Carl B
CB
Yau
King-Wai
KW
Frederick
Jeanne M
JM
Palczewski
Krzysztof
K
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
D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase; C484780:Gucy2e protein, mouse; C484783:Gucy2f protein, mouse