Laidlaw, Kamilla M E orcid.org/0000-0001-9209-4806, Paine, Katherine M, Bisinski, Daniel D et al. (6 more authors) (2022) Endosomal cargo recycling mediated by Gpa1 and phosphatidylinositol 3-kinase is inhibited by glucose starvation. Molecular Biology of the Cell. ar31. ISSN 1059-1524
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2022 Laidlaw, Paine, et al. |
Keywords: | 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 |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 07 Jul 2022 14:40 |
Last Modified: | 10 Nov 2024 01:28 |
Published Version: | https://doi.org/10.1091/mbc.E21-04-0163 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1091/mbc.E21-04-0163 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188830 |