Immunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase

• DOI: 10.1126/sciadv.adi5545
• Publication Date: 2023-12-06T18:59:41Z
• Authors: Matthew J. Fanelli; Christofer M. Welsh; Dominique S. Lui; Lorissa J. Smulan; Amy K. Walker
• Keywords: Animals; Golgi Apparatus; ADP-Ribosylation Factor 1; Biological Transport; Biomedicine and Life Sciences; Caenorhabditis elegans; GTP Phosphohydrolases

Infection response and other immunity-linked genes (ILGs) were first named in Caenorhabditis elegans-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why attack metabolic changes both increase ILGs unclear. We find that activated phosphatidylcholine (PC) levels change membranes of secretory organelles C. elegans. RNAi targeting the ADP-ribosylation factor arf-1, which disrupts Golgi function, activates ILGs. Low PC limits ARF-1 suggesting a mechanism for ILG activation via metabolism, as part membrane stress acting outside ER. selected uncovered defects secretion two GFP reporters accumulation pathogen-responsive complement C1r/C1s, Uegf, Bmp1 (CUB) domain fusion protein. Our data argue up-regulation some coordinated to trafficking may act counteract on function.