Calmodulin permanently associates with rat olfactory CNG channels under native conditions.
An important mechanism by which vertebrate olfactory sensory neurons rapidly adapt to odorants is feedback modulation of the Ca(2+)-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 Ca(2+)-free calmodulin (apocalmodulin), which is then poised to trigger inhibition of native channels in the presence of Ca(2+).
Bradley
Jonathan
J
Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA. jbradley@jhu.edu
Bönigk
Wolfgang
W
Yau
King-Wai
KW
Frings
Stephan
S
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004622:Embryo, Mammalian; D025461:Feedback, Physiological; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney; D008564:Membrane Potentials / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009830:Olfactory Bulb / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection / Q000379:methods
D002147:Calmodulin; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D011994:Recombinant Proteins; D000242:Cyclic AMP; D002118:Calcium