Related Experiment Video

Updated: Sep 20, 2026

Dissection of Local Ca2+ Signals in Cultured Cells by Membrane-targeted Ca2+ Indicators
11:33

Dissection of Local Ca2+ Signals in Cultured Cells by Membrane-targeted Ca2+ Indicators

Published on: March 22, 2019

Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels

Jie Zheng1, Michael D Varnum, William N Zagotta

  • 1Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195-7290, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|September 5, 2003
PubMed

Insights

Calcium-calmodulin binding to olfactory channels causes domain separation, leading to olfactory adaptation. This structural change explains how smell sensitivity decreases with prolonged odorant exposure.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Sensory Physiology

Background:

  • Cyclic nucleotide-gated channels are crucial for smell signal processing.
  • Olfactory adaptation, or reduced sensitivity after odorant exposure, is linked to channel regulation.

Purpose of the Study:

  • To investigate the structural mechanism of olfactory adaptation in cyclic nucleotide-gated channels.
  • To visualize real-time domain interactions within these channels.

Main Methods:

  • Utilized fluorescence resonance energy transfer (FRET) with enhanced cyan and yellow fluorescent proteins.
  • Genetically attached fluorescent proteins to specific channel domains in intact cells and excised patches.

Main Results:

  • Confirmed specific inter-subunit domain interactions within cyclic nucleotide-gated channels.
  • Observed a decrease in FRET upon Ca2+-calmodulin binding, correlating with channel downregulation.
  • Demonstrated that Ca2+-calmodulin binding causes domain separation or reorientation.

Conclusions:

  • Ca2+-calmodulin binding induces structural changes in cyclic nucleotide-gated channels, mediating olfactory adaptation.
  • The study provides a structural basis for understanding the molecular mechanisms of olfactory adaptation.

More Related Videos

Pull-down of Calmodulin-binding Proteins07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis00:09

Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis

Published on: February 18, 2020

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Intracellular Signaling Cascades01:43

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...