GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice

Kim A. Howes, Mark E. Pennesi, Izabela Sokal, Jill Church-Kopish, Ben Schmidt, David Margolis, Jeanne M. Frederick, Fred Rieke, Krzysztof Palczewski, Samuel M. Wu, Peter B. Detwiler, Wolfgang Baehr

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1545-1554
Number of pages10
JournalEMBO Journal
Volume21
Issue number7
DOIs
StatePublished - Apr 2 2002

Keywords

  • Guanylate cyclase-activating proteins
  • Paired flash electroretinograms
  • Rod photoreceptors
  • Single cell recordings
  • Visual transduction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Howes, K. A., Pennesi, M. E., Sokal, I., Church-Kopish, J., Schmidt, B., Margolis, D., Frederick, J. M., Rieke, F., Palczewski, K., Wu, S. M., Detwiler, P. B., & Baehr, W. (2002). GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice. EMBO Journal, 21(7), 1545-1554. https://doi.org/10.1093/emboj/21.7.1545