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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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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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COP Coated Vesicles00:59

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Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Related Experiment Video

Updated: Jun 2, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking.

Ryan M Loughran1, Gurpreet K Arora1, Jiachen Sun2

  • 1Cancer Center, Sanford Burnham Prebys Medical Discovery Institute; La Jolla, CA, USA.

Biorxiv : the Preprint Server for Biology
|January 13, 2025
PubMed
Summary
This summary is machine-generated.

This study reveals that PI5P4Ks are crucial for lysosomal cholesterol transport and mTOR signaling in p53-deficient cancers. Targeting PI5P4Ks offers a new strategy to disrupt cholesterol homeostasis and combat cancer growth.

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Last Updated: Jun 2, 2025

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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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Quantification of Endosome and Lysosome Motilities in Cultured Neurons Using Fluorescent Probes
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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • p53-deficient cancers exhibit dysregulated cholesterol metabolism via sterol regulatory element-binding protein 2 (SREBP-2) pathways.
  • Statins targeting cholesterol synthesis show promise but face acquired resistance.
  • New strategies are needed to inhibit both cholesterol synthesis and intracellular transport.

Purpose of the Study:

  • To investigate the role of Phosphoinositide 5-phosphate 4-kinases (PI5P4Ks) in cholesterol homeostasis.
  • To elucidate the mechanism by which PI5P4Ks regulate lysosomal cholesterol transport and mTOR signaling.
  • To explore PI5P4Ks as a therapeutic target in p53-deficient cancers.

Main Methods:

  • Investigated the enzymatic activity of PI5P4Ks in converting PI(5)P to PI(4,5)P2.
  • Assessed the impact of PI5P4Ks on lysosomal cholesterol transport and positioning.
  • Analyzed the connection between PI5P4Ks, mTOR pathway signaling, and tumor proliferation.

Main Results:

  • PI5P4Ks facilitate intracellular lysosomal cholesterol transport.
  • PI5P4Ks regulate lysosome positioning within the cell.
  • PI5P4Ks sustain growth signaling through the mTOR pathway in p53-deficient contexts.
  • This study identifies PI5P4Ks as an upstream regulator unifying previously observed phenomena.

Conclusions:

  • PI5P4Ks are critical regulators of cholesterol transport and mTOR signaling.
  • Targeting PI5P4Ks presents a novel therapeutic strategy for p53-deficient cancers.
  • Understanding PI5P4K function provides new insights into cholesterol homeostasis in cancer.