1. The erlin1/erlin2 complex binds to and stabilizes phosphatidylinositol 3-phosphate and regulates autophagy.
- Author
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Hua F, Bonzerato CG, Keller KR, Guo D, Luo J, and Wojcikiewicz RJH
- Subjects
- Humans, HeLa Cells, Membrane Proteins metabolism, Protein Binding, Class III Phosphatidylinositol 3-Kinases metabolism, Endoplasmic Reticulum metabolism, Autophagy, Phosphatidylinositol Phosphates metabolism
- Abstract
The erlin1/erlin2 (E1/E2) complex is an endoplasmic reticulum membrane-located assemblage of the proteins erlin1 and erlin2. Here, we demonstrate direct and selective binding of phosphatidylinositol 3-phosphate (PI(3)P) to recombinant erlins and that disruption or deletion of the E1/E2 complex reduces HeLa cell PI(3)P levels by ∼50 %. This reduction correlated with a decrease in autophagic flux, with no effect on the endocytic pathway, and was not due to reduced VPS34 kinase activity, which is critical for maintaining steady-state PI(3)P levels. Pharmacological inhibition of VPS34 and suppression of PI(3)P levels caused a similar reduction in autophagic flux. Overall, these data indicate that by binding to PI(3)P, the E1/E2 complex plays an important role in maintaining the steady-state levels of PI(3)P and, thus, sustains some key PI(3)P-dependent processes, e.g., autophagy., Competing Interests: Declaration of competing interest None. The authors have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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