Facilitation of Calmodulin-Mediated Odor Adaptation by cAMP-Gated Channel Subunits

@article{Bradley2001FacilitationOC,
  title={Facilitation of Calmodulin-Mediated Odor Adaptation by cAMP-Gated Channel Subunits},
  author={Jonathan Bradley and Dirk Reuter and Stephan Frings},
  journal={Science},
  year={2001},
  volume={294},
  pages={2176 - 2178}
}
Calcium (Ca2+) influx through Ca2+-permeable ion channels plays a pivotal role in a variety of neuronal signaling processes, and negative-feedback control of this influx by Ca2+ itself is often equally important for modulation of such signaling. Negative modulation by Ca2+ through calmodulin (CaM) on cyclic nucleotide–gated (CNG) channels underlies the adaptation of olfactory receptor neurons to odorants. We show that this feedback requires two additional subunits of the native olfactory… 
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TLDR
The targeted deletion of the mouse CNGA4gene, which encodes a modulatory CNG subunit, results in a defect in odorant-dependent adaptation and accelerates the Ca2+-mediated negative feedback in olfactory signaling and allows rapid adaptation in this sensory system.
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TLDR
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TLDR
Recent advances in understanding the subunit composition and the mechanisms and roles for Ca2+/CaM-dependent inhibition in olfactory and rod CNG channels are reviewed.
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TLDR
Most vertebrate olfactory receptor neurons share a common G-protein-coupled pathway for transducing the binding of odorant into depolarization, and the relation between stimulus strength and receptor current shows positive cooperativity.
Dynamics of Ca2+-Calmodulin–dependent Inhibition of Rod Cyclic Nucleotide-gated Channels Measured by Patch-clamp Fluorometry
TLDR
Results show that Ca(2+)/CaM binds directly to CNG channels, and that binding is the rate-limiting step for channel inhibition, consistent with the notion that rearrangement of the NH(2)- and COOH-terminal regions underlies Ca( 2+)/ CaM-dependent inhibition.
The Ca-activated Cl Channel and its Control in Rat Olfactory Receptor Neurons
TLDR
It is demonstrated that a given Cl channel is activated by Ca2+ originating from multiple CNG channels, thus allowing low-noise amplification of the olfactory receptor current.
Regulation of cyclic nucleotide-gated channels
Distinct binding properties distinguish LQ-type calmodulin-binding domains in cyclic nucleotide-gated channels.
TLDR
The data provide biochemical evidence against a contribution of CNGA4 to feedback inhibition and indicate that feedback control is the exclusive role of the B-subunits in photoreceptors and olfactory receptor neurons.
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References

SHOWING 1-10 OF 18 REFERENCES
Central Role of the CNGA4 Channel Subunit in Ca2+-Calmodulin-Dependent Odor Adaptation
TLDR
The targeted deletion of the mouse CNGA4gene, which encodes a modulatory CNG subunit, results in a defect in odorant-dependent adaptation and accelerates the Ca2+-mediated negative feedback in olfactory signaling and allows rapid adaptation in this sensory system.
Calcium-Calmodulin Modulation of the Olfactory Cyclic Nucleotide-Gated Cation Channel
TLDR
Study of the olfactory cyclic nucleotide-activated cation channel, which is modulated by calcium-calmodulin, indicates that calcium-Calmodulin directly binds to a specific domain on the amino terminus of the channel, revealing a control mechanism that resembles those underlying the regulation of enzymes by calmodulin.
Phosphorylation of Mammalian Olfactory Cyclic Nucleotide-Gated Channels Increases Ligand Sensitivity
TLDR
The results of this study provide information about the control of ligand sensitivity in olfactory CNG channels by an intrinsic regulatory domain, representing both a calmodulin-binding site and a substrate for PKC.
Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP.
TLDR
The cloning and characterization of a second rat cng channel subunit, denoted rOCNC2, is described, which indicates that the native olfactory cNG channel is likely to be a heterooligomer of the r OCNC1 and rOC NC2 subunits.
Properties of cyclic nucleotide-gated channels mediating olfactory transduction. Activation, selectivity, and blockage
Cyclic nucleotide-gated channels (cng channels) in the sensory membrane of olfactory receptor cells, activated after the odorant-induced increase of cytosolic cAMP concentration, conduct the receptor
Ca2+ permeation in cyclic nucleotide‐gated channels
TLDR
Ca2+ permeation is controlled by the Ca2+‐binding affinity of the intrapore cation‐binding site, which varies profoundly between members of the CNG channel family, and gives rise to a surprising diversity in the ability to generate Ca2- signals.
Mechanism of odorant adaptation in the olfactory receptor cell
TLDR
The nature of the adaptational mechanism in intact olfactory cells is investigated by using a combination of odorant stimulation and cAMP photolysis which produces current responses that bypass the early stages of signal transduction (involving the receptor, G protein and adenylyl cyclase).
Interdomain interactions underlying activation of cyclic nucleotide-gated channels.
TLDR
The amino-terminal domain may promote channel opening by directly interacting with the carboxyl- terminal gating machinery; calmodulin regulates channel activity by targeting this interaction.
The cellular and molecular basis of odor adaptation.
TLDR
Evidence is provided for the involvement of distinct molecular steps in at least two rapid forms and one persistent form of odor adaptation that coexist in vertebrate olfactory receptor neurons, indicating that they are controlled, at least in part, by separate molecular mechanisms.
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