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GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice
被引:92
作者:
Howes, KA
Pennesi, ME
Sokal, I
Church-Kopish, J
Schmidt, B
Margolis, D
Frederick, JM
Rieke, F
Palczewski, K
Wu, SM
Detwiler, PB
Baehr, W
[1
]
机构:
[1] Univ Utah, Hlth Sci Ctr, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT 84112 USA
[2] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA
[3] Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA
[5] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA
[6] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA
[7] Univ Washington, Dept Pharmacol & Chem, Seattle, WA 98195 USA
[8] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[9] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84112 USA
关键词:
guanylate cyclase-activating proteins;
paired flash electroretinograms;
rod photoreceptors;
single cell recordings;
visual transduction;
D O I:
10.1093/emboj/21.7.1545
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca2+ and cGMP. Ca2+ 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.
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页码:1545 / 1554
页数:10
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