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Endosomal cargo recycling mediated by Gpa1 and phosphatidylinositol 3-kinase is inhibited by glucose starvation

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JournalMolecular Biology of the Cell
DateAccepted/In press - 21 Jan 2022
DateE-pub ahead of print - 17 Mar 2022
DatePublished (current) - 1 Apr 2022
Issue number4
Volume33
Number of pages18
Early online date17/03/22
Original languageEnglish

Abstract

Cell surface protein trafficking is regulated in response to nutrient availability, with multiple pathways directing surface membrane proteins to the lysosome for degradation in response to suboptimal extracellular nutrients. Internalized protein and lipid cargoes recycle back to the surface efficiently in glucose-replete conditions, but this trafficking is attenuated following glucose starvation. We find that cells with either reduced or hyperactive phosphatidylinositol 3-kinase (PI3K) activity are defective for endosome to surface recycling. Furthermore, we find that the yeast Gα subunit Gpa1, an endosomal PI3K effector, is required for surface recycling of cargoes. Following glucose starvation, mRNA and protein levels of a distinct Gα subunit Gpa2 are elevated following nuclear translocation of Mig1, which inhibits recycling of various cargoes. As Gpa1 and Gpa2 interact at the surface where Gpa2 concentrates during glucose starvation, we propose that this disrupts PI3K activity required for recycling, potentially diverting Gpa1 to the surface and interfering with its endosomal role in recycling. In support of this model, glucose starvation and overexpression of Gpa2 alter PI3K endosomal phosphoinositide production. Glucose deprivation therefore triggers a survival mechanism to increase retention of surface cargoes in endosomes and promote their lysosomal degradation.

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© 2022 Laidlaw, Paine, et al.

    Research areas

  • Endosomes/metabolism, GTP-Binding Protein alpha Subunits/genetics, Glucose/metabolism, Membrane Proteins/metabolism, Phosphatidylinositol 3-Kinase/metabolism, Phosphatidylinositol 3-Kinases/metabolism, Protein Transport, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism

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