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Endocytic tethers modulate unconventional GAPDH secretion.

Michael J Cohen1,2, Brianne Philippe1, Peter N Lipke1,2

  • 1Biology Department, Brooklyn College of the City University of New York, Brooklyn, NY 11210, USA.

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Summary
This summary is machine-generated.

Unconventionally secreted yeast proteins, like glyceraldehyde-3-phosphate dehydrogenase (GAPDH), use uncharacterized pathways. Entry into the endolysosomal system is crucial for this non-conventional secretion of GAPDH.

Keywords:
CORVET tetherESCRT complexEndolysosomal secretion systemHOPS tetherMoonlighting proteinMultivesicular bodyYeast cell wall

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Yeast cell walls host classically and unconventionally secreted proteins.
  • Unconventional secretion bypasses the endoplasmic reticulum (ER) via unknown mechanisms.
  • Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme, is found in the cytosol and cell wall.

Purpose of the Study:

  • To investigate the mechanisms of unconventional protein secretion in yeast.
  • To identify genes involved in the secretion of cell wall-associated GAPDH.
  • To determine the role of the endolysosomal system in GAPDH secretion.

Main Methods:

  • Screening of homozygous gene deletion mutants in *Saccharomyces cerevisiae* for altered cell wall GAPDH activity.
  • Analysis of GAPDH localization using cell imaging techniques.
  • Investigating the impact of endosomal protein Vps21 on GAPDH secretion and endosomal trafficking.

Main Results:

  • Gene deletions affecting endocytic tethers in the endolysosomal system (e.g., *vps21, bro1, vps41, pep12*) significantly impacted GAPDH secretion.
  • The primary GAPDH isoform, Tdh3, was found in endolysosomal compartments, including multivesicular bodies.
  • Deletion of the endosomal Rab5-GTPase Vps21 impaired GAPDH secretion and delayed endosomal compartment entry.

Conclusions:

  • The endolysosomal system plays a critical role in the unconventional secretion of GAPDH.
  • Entry into endolysosomal compartments facilitates the non-conventional secretion pathway for GAPDH.
  • This study elucidates a novel secretion route for cytosolic proteins to the yeast cell wall.