SRF3 couples cellular iron homeostasis and defense responses through ubiquitin-dependent nano-organization

Abstract

Iron homeostasis is a central component of host defense responses. In mammals, iron availability is rapidly adjusted through receptor mediated pathways, whereas it remains unclear how plants regulate iron homeostasis during the earliest stages of immune activation. Here, we identify a rapid iron regulatory mechanism centered on the plasma membrane receptor kinase STRUBBELIG RECEPTOR FAMILY 3 (SRF3), which integrates bacterial immune signaling with ferrous iron homeostasis. Perception of flagellin triggers a burst of reactive oxygen species that induces a rapid and transient depletion of the labile ferrous iron pool. This state promotes SRF3 ubiquitination and clathrin-dependent endocytosis, a process required to restore intracellular ferrous iron levels while dampening immune responses. Using super resolution microscopy, we show that this functional integration relies on ubiquitin dependent nano organization of SRF3 at the plasma membrane, enabling distinct signaling outputs from a single receptor. Thereby, SRF3 modulates both immune signaling and the proliferation of commensal and pathogenic bacteria. Together, our findings uncover a fast-acting iron homeostasis pathway in plants that dynamically couples nutrient availability with immunity, thereby shaping host microbe interactions at the onset of infection.