TY - JOUR
T1 - The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors
AU - Baehr, Wolfgang
AU - Karan, Sukanya
AU - Maeda, Tadao
AU - Luo, Dong Gen
AU - Li, Sha
AU - Bronson, J. Darin
AU - Watt, Carl B.
AU - Yau, King Wai
AU - Frederick, Jeanne M.
AU - Palczewski, Krzysztof
PY - 2007/3/23
Y1 - 2007/3/23
N2 - 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 α-subunit were mostly unaffected. Outer segment membranes of GC1-/- and GC double knock-out cones were destabilized and devoid of cone transducin (α- and γ-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.
AB - 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 α-subunit were mostly unaffected. Outer segment membranes of GC1-/- and GC double knock-out cones were destabilized and devoid of cone transducin (α- and γ-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.
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U2 - 10.1074/jbc.M610369200
DO - 10.1074/jbc.M610369200
M3 - Article
C2 - 17255100
AN - SCOPUS:34247843072
SN - 0021-9258
VL - 282
SP - 8837
EP - 8847
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -