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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...
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...
What are Second Messengers?01:12

What are Second Messengers?

Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...

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Related Experiment Video

Updated: Jun 27, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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

Published on: July 26, 2019

Phosphoinositides regulate P2X4 ATP-gated channels through direct interactions.

Louis-Philippe Bernier1, Ariel R Ase, Stéphanie Chevallier

  • 1Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada H3A 2B4.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|November 28, 2008
PubMed
Summary

Phosphoinositides, specifically PI(4,5)P(2) and PI(3,4,5)P(3), regulate P2X(4) channel function and calcium permeability. These findings reveal direct lipid interactions crucial for neuropathic pain mechanisms.

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

Published on: October 15, 2016

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
16:36

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 18, 2009

Related Experiment Videos

Last Updated: Jun 27, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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 Probes
07:26

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

Published on: October 15, 2016

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
16:36

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 18, 2009

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • P2X receptors, particularly P2X(4), are implicated in neuropathic pain and inflammatory responses.
  • Posttranslational regulation of P2X(4) channel function is critical but not well understood.

Purpose of the Study:

  • To investigate the role of phosphoinositides, phosphatidylinositol 4,5-bisphosphate (PIP(2)) and phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in modulating P2X(4) receptor function.
  • To elucidate the direct interactions between phosphoinositides and the P2X(4) channel.

Main Methods:

  • Utilized wortmannin to deplete intracellular PIP(2) and PIP(3) levels in microglial cells and oocytes.
  • Performed patch clamp recordings and ratiometric ion imaging to measure P2X(4) channel activity and calcium influx.
  • Conducted in vitro binding assays to assess direct phospholipid-channel interactions.

Main Results:

  • Depletion of PIP(2) and PIP(3) significantly reduced P2X(4) current amplitude and calcium entry.
  • Wortmannin treatment altered P2X(4) channel kinetics, reduced ATP efficacy, and impaired recovery from desensitization.
  • Direct binding of phospholipids to the P2X(4) C-terminal domain was confirmed.

Conclusions:

  • Signaling phosphoinositides PIP(2) and PIP(3) play novel regulatory roles in P2X(4) channel function.
  • Direct channel-lipid interactions are a key mechanism underlying P2X(4) modulation.
  • These findings offer insights into the cellular mechanisms of neuropathic pain.