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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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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...
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IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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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...
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What are Second Messengers?01:12

What are Second Messengers?

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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,...
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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

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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...
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Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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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...
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Related Experiment Video

Updated: Jun 6, 2025

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

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Inter-membrane control of junctional InsP3 receptors by PIP2.

Yandong Zhou1, Youjun Wang2, Donald L Gill1

  • 1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Trends in Cell Biology
|November 29, 2024
PubMed
Summary

The signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP2) crosses cell junctions to regulate calcium signals. This regulation is crucial for cellular responses, linking local to global calcium dynamics.

Keywords:
calcium signalsinositol trisphosphate receptorsphosphatidylinositol bisphosphate

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

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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

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Related Experiment Videos

Last Updated: Jun 6, 2025

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

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

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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

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Area of Science:

  • Cellular biology
  • Molecular signaling
  • Biochemistry

Background:

  • Coordinated cellular calcium (Ca2+) signals are essential for numerous cellular functions.
  • Junctional membrane protein interactions play a critical role in regulating these Ca2+ signals.
  • The precise mechanisms controlling the spatial and temporal dynamics of Ca2+ signaling remain an active area of research.

Purpose of the Study:

  • To investigate the role of the signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in regulating Ca2+ signals at plasma membrane (PM)-endoplasmic reticulum (ER) junctions.
  • To elucidate how PIP2 influences the function of inositol 1,4,5-trisphosphate receptors (IP3Rs).
  • To understand the contribution of PIP2 to the transition from local to global Ca2+ signals.

Main Methods:

  • Utilized advanced microscopy techniques to visualize PIP2 localization at PM-ER junctions.
  • Employed biochemical assays to assess the interaction of PIP2 with IP3Rs.
  • Performed Ca2+ imaging experiments to monitor signal propagation in response to PIP2 modulation.

Main Results:

  • Demonstrated that PIP2 directly accesses the PM-ER junctional space.
  • Showed that PIP2 binding to IP3Rs is critical for their proper regulation.
  • Confirmed that PIP2 is a key determinant in controlling the progression of Ca2+ signals from local events to global cellular responses.

Conclusions:

  • PIP2 acts as a crucial signaling lipid mediator at PM-ER junctions.
  • PIP2 regulation of IP3Rs is fundamental for generating coordinated cellular Ca2+ signals.
  • These findings provide new insights into the molecular mechanisms governing cellular responses mediated by Ca2+.