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Calmodulin permanently associates with rat olfactory CNG channels under native conditions

Nature Neuroscience volume 7, pages 705–710 (2004)Cite this article

Abstract

An important mechanism by which vertebrate olfactory sensory neurons rapidly adapt to odorants is feedback modulation of the Ca2+-permeable cyclic nucleotide–gated (CNG) transduction channels. Extensive heterologous studies of homomeric CNGA2 channels have led to a molecular model of channel modulation based on the binding of calcium-calmodulin to a site on the cytoplasmic amino terminus of CNGA2. Native rat olfactory CNG channels, however, are heteromeric complexes of three homologous but distinct subunits. Notably, in heteromeric channels, we found no role for CNGA2 in feedback modulation. Instead, an IQ-type calmodulin-binding site on CNGB1b and a similar but previously unidentified site on CNGA4 are necessary and sufficient. These sites seem to confer binding of Ca2+-free calmodulin (apocalmodulin), which is then poised to trigger inhibition of native channels in the presence of Ca2+.

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Figure 1: Ca2+-dependent inhibition of native rat olfactory CNG channels.
Figure 2: Calmodulin preassociates with CNGA2-A4-B1b channels.
Figure 3: Ca2+-CaM modulation of CNGA2-A4-B1b channels does not involve the N-terminal Baa motif of CNGA2.
Figure 4: Calmodulin-binding sites in CNGB1b and CNGA4 that mediate Ca2+-CaM modulation of CNGA2-A4-B1b channels.

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Acknowledgements

We thank J. Reisert and V. Bhandawat for many discussions; J. Kehoe, B. Barbour, N. Pardigon, J. Lynch, S. Hattar, R. Kuruvilla and P. Bauer for comments; P. Ascher for critically reading the manuscript and V. Kefelov for suggesting the experiment for Figure 2c. J.B. dedicates this paper to Norman Davidson. This work was supported by the Deutsche Forschungsgemeinschaft under grant SPP 1025 (S.F.) and by the Howard Hughes Medical Institute (J.B. & K.-W.Y.).

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  1. Stephan Frings

    Present address: Department of Molecular Physiology, University of Heidelberg, Im Neuenheimer Feld 230, 69120, Heidelberg, Germany

Authors and Affiliations

  1. Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Jonathan Bradley & King-Wai Yau

  2. Institute for Biological Information Processing, Forschungszentrum Jülich, Leo-Brand-Strasse, Jülich, 52425, Germany

    Wolfgang Bönigk & Stephan Frings

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Correspondence to Jonathan Bradley or Stephan Frings.

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Bradley, J., Bönigk, W., Yau, KW. et al. Calmodulin permanently associates with rat olfactory CNG channels under native conditions. Nat Neurosci 7, 705–710 (2004). https://doi.org/10.1038/nn1266

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