Balancing roles between phosphatidylinositols and sphingolipids in regulating immunity and ER stress responses in pi4kβ1,2

SUMMARY Plant immune regulation is complex. In addition to proteins, lipid molecules play critical roles in modulating immune responses. The mutant pi4kβ1,2 is mutated in two phosphatidylinositol 4‐kinases PI4Kβ1 and β2 involved in the biosynthesis of phosphatidylinositol 4‐phosphate (PI4P). The mutant displays autoimmunity, short roots, aberrant root hairs, and a heightened sensitivity to ER stress. In a forward genetic screen designed to dissect pi4kβ1,2 autoimmunity, we found that Orosomucoid‐like 1 (ORM1) is required for the phenotypes of pi4kβ1,2, including short root and ER stress sensitivity. The orm1 mutations lead to increased long‐chain base and ceramide levels in the suppressors. We also found that the basic region/leucine Zipper motif (bZIP) 28 and 60 transcription factors, central regulators of ER stress response, are required for its autoimmunity and root defect. In comparison, the defense‐related phytohormones salicylic acid (SA) and N‐hydroxypipecolic acid (NHP) are required for its autoimmunity but plays a minor role in its root phenotypes. Further, we found that wild‐type plants overexpressing ORM1 are autoimmune, displaying short roots and increased ceramide levels. The autoimmunity of the ORM1 overexpression lines is dependent on SA, NHP, and bZIP60. As ORM1 is a known negative regulator of sphingolipid biosynthesis, our study uncovers a balancing role between PIs and sphingolipids in regulating immunity and ER stress responses in pi4kβ1,2. Significance Statement By studying the ER stress response and immunity defects of lipid mutants, a potential balancing role between phosphatidylinositols and sphingolipids in regulating immunity and ER stress responses was uncovered. This will provide opportunity to alter lipid homeostasis to optimize plants' ability to be more resilient against biotic and abiotic stresses.