Endocytic tethers modulate unconventional GAPDH secretion

Yeast cell walls contain both classically-secreted and unconventionally-secreted proteins. The latter class lacks the signal sequence for translocation into the ER, therefore these proteins are transported to the wall by uncharacterized mechanisms. One such protein is the glycolytic enzyme glycerald...

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Bibliographic Details
Published in:Cell surface (Amsterdam) 2025-06, Vol.13, p.100138, Article 100138
Main Authors: Cohen, Michael J., Philippe, Brianne, Lipke, Peter N.
Format: Article
Language:English
Subjects:
CORVET tether
Endolysosomal secretion system
ESCRT complex
HOPS tether
Moonlighting protein
Multivesicular body
Research Paper
Yeast cell wall
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Summary:Yeast cell walls contain both classically-secreted and unconventionally-secreted proteins. The latter class lacks the signal sequence for translocation into the ER, therefore these proteins are transported to the wall by uncharacterized mechanisms. One such protein is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which is abundant in the cytosol, but also found in the yeast cell wall where it is enzymatically active. We screened diploid Saccharomyces cerevisiae homozygous gene deletions for changes in cell wall GAPDH activity. Deletions targeting endocytic tethers in the endolysosomal system had the largest effects on GAPDH secretion, including vps21, bro1, vps41, and pep12. The predominant GAPDH isoform Tdh3 was partially localized to endolysosomal compartments, including multivesicular bodies, which are common entry points to unconventional protein secretion pathways. Yeast lacking the endosomal Rab5-GTPase Vps21 had defects in GAPDH secretion as well as delayed entry into to the endolysosomal compartments. Therefore, we conclude that entry into the endolysosomal compartment facilitates non-conventional secretion of GAPDH.
ISSN:2468-2330
2468-2330
DOI:10.1016/j.tcsw.2024.100138