GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice.
Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca(2+) and cGMP. Ca(2+) regulates the activity of guanylate cyclase (GC) and the synthesis of cGMP by acting on a GC-activating protein (GCAP). While this action is critical for rapid termination of the light response, the GCAP responsible has not been identified. To test if GCAP1, one of two GCAPs present in mouse rods, supports the generation of normal flash responses, transgenic mice were generated that express only GCAP1 under the control of the endogenous promoter. Paired flash responses revealed a correlation between the degree of recovery of the rod a-wave and expression levels of GCAP1. In single cell recordings, the majority of the rods generated flash responses that were indistinguishable from wild type. These results demonstrate that GCAP1 at near normal levels supports the generation of wild-type flash responses in the absence of GCAP2.
Howes
Kim A
KA
Department of Ophthalmology, Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84112-5330, USA.
Pennesi
Mark E
ME
Sokal
Izabela
I
Church-Kopish
Jill
J
Schmidt
Ben
B
Margolis
David
D
Frederick
Jeanne M
JM
Rieke
Fred
F
Palczewski
Krzysztof
K
Wu
Samuel M
SM
Detwiler
Peter B
PB
Baehr
Wolfgang
W
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000378:metabolism*; D051604:Guanylate Cyclase-Activating Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D002135:Calcium-Binding Proteins; D051604:Guanylate Cyclase-Activating Proteins; C496737:Guca1a protein, mouse; C496740:Guca1b protein, mouse; D006162:Guanylate Cyclase