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Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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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.
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GPCR Desensitization01:12

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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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...
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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.
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Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
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G-Protein Gated Ion Channels01:21

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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.
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Related Experiment Video

Updated: Jan 16, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

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Calmodulin binding is required for calcium mediated TRPA1 desensitization.

Justin H Sanders1, Camila Garcia1, Kehinde M Taiwo1

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

Nature Communications
|October 1, 2025
PubMed
Summary

Calmodulin (CaM) binds the TRPA1 channel at rest, suppressing its activity. This Ca2+/CaM interaction is crucial for TRPA1 channel function, particularly for rapid desensitization.

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Cell-based Calcium Assay for Medium to High Throughput Screening of TRP Channel Functions using FlexStation 3

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Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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Cell-based Calcium Assay for Medium to High Throughput Screening of TRP Channel Functions using FlexStation 3
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Area of Science:

  • Ion channel physiology
  • Molecular neuroscience
  • Calcium signaling

Background:

  • TRPA1 channels are vital for pain and inflammation signaling.
  • TRPA1 exhibits complex calcium (Ca2+) regulation, including potentiation and desensitization.
  • The precise mechanisms of Ca2+ regulation in TRPA1 remain elusive.

Purpose of the Study:

  • To elucidate the role of Calmodulin (CaM) in TRPA1 channel activity.
  • To identify the Ca2+/CaM binding site on TRPA1.
  • To understand how Ca2+/CaM binding influences TRPA1 channel gating and desensitization.

Main Methods:

  • Biochemical assays
  • Biophysical techniques
  • Computational modeling
  • Nuclear Magnetic Resonance (NMR) spectroscopy
  • Cellular electrophysiology

Main Results:

  • Calmodulin (CaM) binds to the TRPA1 channel in resting cells, inhibiting its activity.
  • A conserved high-affinity Ca2+/CaM binding site was identified in the TRPA1 C-terminus.
  • Disrupting Ca2+/CaM binding leads to hyperactive TRPA1 channels with significantly slowed desensitization.
  • Higher extracellular Ca2+ partially restored normal desensitization rates.

Conclusions:

  • Calmodulin (CaM) acts as an essential auxiliary subunit for TRPA1 channels.
  • Ca2+/CaM binding at the distal C-terminus is critical for initiating rapid TRPA1 desensitization via allosteric regulation.
  • This interaction highlights the importance of intrinsically disordered regions in channel function.