Nature Neuroscience7, 705 - 710 (2004)
Published online: 13 June 2004; | doi:10.1038/nn1266
Calmodulin permanently associates with rat olfactory CNG channels under native conditions
Jonathan Bradley1, Wolfgang Bönigk2, King-Wai Yau1
& Stephan Frings2, 3
1
Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
2
Institute for Biological Information Processing, Forschungszentrum Jülich, Leo-Brand-Strasse, 52425 Jülich, Germany.
3
Present address: Department of Molecular Physiology, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.
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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