Related Experiment Video

Updated: May 20, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

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

Published on: January 7, 2019

Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides

Kyohei Itsuki1, Yuko Imai, Yasushi Okamura

  • 1Department of Physiology, School of Medicine, Fukuoka University, Japan.

Channels (Austin, Tex.)
|July 5, 2012
PubMed

Insights

The study reveals TRPC3/C6/C7 channels are regulated by a self-limiting phosphoinositide signaling pathway. This mechanism, studied using DrVSP, is sensitive to signal strength and may impact cardiovascular and neurological health.

Area of Science:

  • Ion channel physiology
  • Molecular biology
  • Cell signaling

Background:

  • TRPC3/C6/C7 channels are crucial in cellular signaling, activated by phospholipase C (PLC).
  • Their regulatory mechanisms are not fully understood, hindering therapeutic development.
  • Understanding these channels is vital due to their broad physiological roles.

Purpose of the Study:

  • To investigate the self-limiting regulation of TRPC3/C6/C7 channels.
  • To highlight the utility of the danio rerio voltage-sensing phosphatase (DrVSP) as a research tool.
  • To explore the impact of signal strength on channel activity.

Main Methods:

  • Utilized membrane-resident danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 channel regulation.
  • Investigated phosphoinositide (PtdIns(4,5)P(2)) and diacylglycerol (DAG) signaling pathways.
  • Compared the self-limiting regulation of these channels with other known mechanisms.

Main Results:

  • TRPC3/C6/C7 channel activity is controlled by a self-limiting PtdIns(4,5)P(2)-DAG signaling pathway.
  • DrVSP is an effective tool for studying PtdIns(4,5)P(2) regulation and lipid dynamics.
  • Channel regulation is highly sensitive to activation signal strength, affecting channel gating.

Conclusions:

  • The self-limiting regulation of TRPC3/C6/C7 channels is a key feature of their function.
  • DrVSP offers advantages for studying phosphoinositide metabolism-linked channel regulation.
  • Dysfunctional self-limiting regulation may contribute to cardiovascular, gastrointestinal, and neurological diseases.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes07:26

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes

Published on: October 15, 2016

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
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,...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...