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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.
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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IP3/DAG Signaling Pathway01:11

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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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Regulated Protein Degradation02:58

Regulated Protein Degradation

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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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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Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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Related Experiment Video

Updated: Mar 18, 2026

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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Chapter 4 - Inositol 1,4,5-Trisphosphate Receptor Ubiquitination.

F A Wright1, R J H Wojcikiewicz1

  • 1Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, United States.

Progress in Molecular Biology and Translational Science
|July 6, 2016
PubMed
Summary
This summary is machine-generated.

Activated inositol 1,4,5-trisphosphate receptors (IP3Rs) are degraded by the cell. This degradation regulates calcium (Ca2+) signaling and is linked to various diseases when proteins involved in IP3R processing are mutated.

Keywords:
ERIP(3)Rcalcium intracellular releaseneurodegenerative diseaseubiquitin ligase

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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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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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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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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Inositol 1,4,5-trisphosphate receptors (IP3Rs) are tetrameric ion channels in the endoplasmic reticulum membrane.
  • IP3R activation by IP3 and Ca2+ facilitates Ca2+ release, crucial for cellular events like secretion and cell division.

Purpose of the Study:

  • To review recent studies on the degradation of activated IP3Rs by the ubiquitin-proteasome pathway.
  • To elucidate the role of IP3R degradation in regulating cellular Ca2+ responses.
  • To explore the link between IP3R degradation pathway mutations and disease.

Main Methods:

  • Review of recent scientific literature on IP3R function, regulation, and degradation.
  • Analysis of studies investigating protein interactions with activated IP3Rs.
  • Examination of research on IP3R ubiquitination and its functional consequences.

Main Results:

  • Activated IP3Rs undergo conformational changes that target them for degradation via the ubiquitin-proteasome pathway.
  • IP3Rs are modified by various ubiquitin conjugates, influencing their stability and function.
  • This regulated degradation fine-tunes cellular Ca2+ signaling in response to external stimuli.

Conclusions:

  • The degradation of activated IP3Rs is a critical mechanism for regulating intracellular Ca2+ dynamics.
  • Dysregulation of IP3R degradation, due to mutations in associated proteins, is implicated in several human diseases.