Article

The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors.

Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah 84112, USA.
Journal of Biological Chemistry (impact factor: 4.77). 04/2007; 282(12):8837-47. DOI:10.1074/jbc.M610369200 pp.8837-47
Source: PubMed

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.

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Keywords

cone phosphodiesterase
 
cone photoreceptors nonfunctional
 
cone pigments
 
cone transducin
 
cyclic GMP phosphodiesterase
 
deletion
 
down-regulated proteins
 
G protein-coupled receptor kinase 1
 
GC double knock-out cones
 
guanylate cyclase-activating proteins 1
 
individual contributions
 
intrinsic requirement
 
membrane-associated phototransduction proteins
 
Outer segment membranes
 
phototransduction
 
Real time reverse transcription-PCR analyses
 
Retinal guanylate cyclases 1
 
rhodopsin
 
rod outer segments
 
rods