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Related Concept Videos

Phosphoinositides and PIPs01:42

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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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Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
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Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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pH Biosensing by PI4P Regulates Cargo Sorting at the TGN.

John J H Shin1, Peter Liu2, Leslie J Chan2

  • 1Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; MRC Laboratory for Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

Developmental Cell
|January 14, 2020
PubMed
Summary

Phosphatidic acid and phosphatidylinositol 4-phosphate act as pH biosensors. This pH sensing regulates protein sorting and cell growth, linking metabolism to membrane trafficking.

Keywords:
Osh1PH domainsPI4PTat2cytoplasmic pHmembrane contact sitespH biosensingphosphatidylinositol 4-phosphatesterol traffickingtrans-Golgi Network

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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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Area of Science:

  • Cell Biology
  • Lipid Signaling
  • Membrane Trafficking

Background:

  • Phosphoinositides and related lipids are key membrane signaling molecules.
  • Their phosphomonoester headgroups have physiological pKa values, enabling pH sensing.
  • Phosphatidic acid is known to function as a pH biosensor.

Purpose of the Study:

  • To investigate if phosphatidylinositol 4-phosphate (PI4P) also acts as a pH biosensor.
  • To determine the role of PI4P pH biosensing in the yeast trans-Golgi network (TGN).
  • To explore the connection between pH sensing, lipid transfer, and cell growth.

Main Methods:

  • Studied the binding of pleckstrin homology (PH) domains to PI4P in yeast TGN.
  • Assessed the dependence of this binding on intracellular pH.
  • Investigated the role of Osh1, an oxysterol-binding protein (OSBP) family member, in sterol transfer.

Main Results:

  • Binding of PH domains to TGN PI4P is pH-dependent, confirming PI4P as a pH biosensor.
  • This pH biosensing is influenced by nutrient availability.
  • PI4P pH sensing regulates sterol transfer to the TGN by Osh1.

Conclusions:

  • TGN PI4P functions as a pH biosensor, directly linking intracellular pH to membrane trafficking.
  • This mechanism regulates protein sorting and sterol transfer at the TGN.
  • Metabolic status, via pH changes, directly controls cell growth through PI4P-mediated regulation of protein trafficking.