Related Experiment Video

Updated: Jun 26, 2026

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
11:47

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells

Published on: April 3, 2019

PIP(2) regulates the ionic current of P2X receptors and P2X(7) receptor-mediated cell death

Qi Zhao1, Min Yang, Adrian T Ting

  • 1Department of Molecular Physiology, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.

Channels (Austin, Tex.)
|January 20, 2009
PubMed

Insights

Phosphatidylinositol 4,5-bisphosphate (PIP2) activates P2X7 receptors, which are crucial for ATP-mediated cell death. PIP2 regulation offers a new strategy to control cell death pathways involving P2X7 receptors.

Area of Science:

  • Cell biology
  • Molecular pharmacology
  • Ion channel function

Background:

  • P2X7 receptors are ATP-gated cation channels involved in cell permeability, cytokine release, and cell death.
  • Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key membrane lipid regulator of various ion channels.

Purpose of the Study:

  • To investigate the role of PIP2 in regulating P2X7 receptor function and ATP-mediated cell death.
  • To identify molecular determinants of PIP2 interaction with the P2X7 receptor.

Main Methods:

  • Patch-clamp electrophysiology on inside-out patches to assess P2X7 channel activity.
  • Pharmacological manipulation of PIP2 levels (synthesis blockade, hydrolysis induction).
  • Site-directed mutagenesis of P2X7 receptor C-terminus and functional characterization.

Main Results:

  • PIP2 directly activates P2X7 channels and other P2X family members.
  • PIP2 depletion significantly reduces ATP-gated P2X7 currents.
  • Specific positively charged residues in the P2X7 C-terminus are critical for PIP2 interaction.
  • ATP-mediated cell death in HEK cells, T cells, and macrophages is dependent on P2X7-PIP2 interaction.

Conclusions:

  • PIP2 is an essential regulator of P2X7 receptor channel activity.
  • The P2X7 receptor's interaction with PIP2 is crucial for its role in ATP-induced cell death.
  • Targeting the P2X7-PIP2 interaction presents a novel therapeutic approach for controlling cell death.

More Related Videos

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels16:36

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

Published on: May 18, 2009

Related Concept Videos

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...
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...
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,...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...