Extracellular pectin-RALF phase separation mediates FERONIA global signaling function

The FERONIA (FER)-LLG1 co-receptor and its peptide ligand RALF regulate myriad processes for plant growth and survival. Focusing on signal-induced cell surface responses, we discovered that intrinsically disordered RALF triggers clustering and endocytosis of its cognate receptors and FER- and LLG1-dependent endocytosis of non-cognate regulators of diverse processes, thus capable of broadly impacting downstream responses. RALF, however, remains extracellular. We demonstrate that RALF binds the cell wall polysaccharide pectin. They phase separate and recruit FER and LLG1 into pectin-RALF-FER-LLG1 condensates to initiate RALF-triggered cell surface responses. We show further that two frequently encountered environmental challenges, elevated salt and temperature, trigger RALF-pectin phase separation, promiscuous receptor clustering and massive endocytosis, and that this process is crucial for recovery from stress-induced growth attenuation. Our results support that RALF-pectin phase separation mediates an exoskeletal mechanism to broadly activate FER-LLG1-dependent cell surface responses to mediate the global role of FER in plant growth and survival. [Display omitted] •Cell surface pectin-RALF1 phase separation recruits FERONIA-LLG1 into condensates•RALF induces FERONIA-LLG1-dependent promiscuous receptor clustering and endocytosis•RALF1-pectin molecular condensates function as surface sensors for stress signals•FERONIA-LLG1-mediated global endocytosis ensures plant resilience under stress In deciphering the global signaling capacity of FERONIA receptor kinase, Liu, Yeh, et al. discovered an extracellular phase separation process driven by FERONIA peptide ligand RALF-cell wall polysaccharide pectin interaction, which leads to cognate and non-cognate receptor clustering and promiscuous endocytosis as a coping mechanism in response to environmental stressors.