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

• Published in: Biochemical and biophysical research communications 2024-10, Vol.731, p.150397, Article 150397
• Main Authors: Hua, Fanghui, Bonzerato, Caden G., Keller, Katherine R., Guo, Dandan, Luo, Juntao, Wojcikiewicz, Richard J.H.
• Format: Article
• Language: English
• Subjects: Autophagy; Endocytosis; endoplasmic reticulum; Erlin complex; human cell lines; Lipid metabolism; Phosphatidylinositol 3-phosphate
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150397

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. •The erlin complex mediates IP3 receptor degradation, but may play other roles.•Recombinant erlin2 binds selectively to phosphatidylinositol 3-phosphate.•Disruption of the complex reduces phosphatidylinositol 3-phosphate levels.•Disruption of the complex also inhibits autophagy, but not the endocytic pathway.