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The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins
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IST1 regulates select recycling pathways.

Amy K Clippinger1, Teresa V Naismith1, Wonjin Yoo2

  • 1Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, Missouri, USA.

Traffic (Copenhagen, Denmark)
|November 5, 2023
PubMed
Summary
This summary is machine-generated.

The Endosomal Sorting Complex Required for Transports (ESCRT) machinery, particularly IST1, is crucial for endosomal trafficking. IST1 regulates the recycling of key receptors from early endosomes, impacting cellular transport pathways.

Keywords:
AP-1clathrinendosomal sorting complex required for transportsorting nexintransferrin receptor

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Membrane Trafficking

Background:

  • Endosomal Sorting Complex Required for Transports (ESCRT) proteins mediate membrane remodeling, including intraluminal vesicle (ILV) formation.
  • IST1, an ESCRT-III protein, is implicated in diverse endosomal remodeling events beyond ILV formation.

Purpose of the Study:

  • To investigate the role of IST1 and its binding partner CHMP1B in early endosomal trafficking.
  • To elucidate the interaction of IST1 with sorting nexin SNX15 in regulating endosomal recycling pathways.

Main Methods:

  • Depletion studies to assess IST1 function.
  • Live-cell microscopy to analyze protein localization and recruitment dynamics.
  • Kinetic and spatial analyses of protein interactions on endosomes.

Main Results:

  • IST1 and CHMP1B are essential for the scission of early endosomal carriers.
  • IST1 depletion impairs transferrin receptor and mannose 6-phosphate receptor export from early endosomes.
  • IST1 interacts with SNX15 within a distinct clathrin-containing subdomain on the endosomal perimeter.

Conclusions:

  • IST1 plays a significant role in specific recycling pathways originating from early/sorting endosomes.
  • The SNX15-IST1 interaction is critical for regulating endosomal cargo sorting and trafficking.
  • These findings reveal a novel function of IST1 in endosomal recycling.