The erlin1/erlin2 complex binds to and stabilizes phosphatidylinositol 3-phosphate and regulates autophagy.

Autor: Hua F; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Bonzerato CG; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Keller KR; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Guo D; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Luo J; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Wojcikiewicz RJH; Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. Electronic address: wojcikir@upstate.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Oct 30; Vol. 731, pp. 150397. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.bbrc.2024.150397
Abstrakt: 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.)
Databáze: MEDLINE
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