The teneurin TEN-1 and its ligand LRON-11 support microbiota-induced neuroprotection and mechanosensory function in C. elegans

leaving the receptor-ligand interactions that underlie TEN-1 function incompletely understood. Here, we identify Leucine-Rich Repeat Only 11 (LRON-11), a previously uncharacterized cell-adhesion molecule, as the ligand for TEN-1. The high-resolution cryoelectron microscopy (cryo-EM) structure of the TEN-1-LRON-11 complex reveals that the leucine-rich repeat domain of LRON-11 directly engages the transthyretin (TTR) domain of TEN-1 through a previously unrecognized interaction interface. Tissue-specific genetic analyses demonstrate that TEN-1 and LRON-11 are required for microbiota-mediated neuroprotection, and structure-guided interface mutations disrupting TEN-1-LRON-11 binding impair normal touch responses in vivo. Together, our findings establish a conserved receptor-ligand signaling axis that supports microbiota-mediated neuroprotection and normal touch responses, revealing how a single receptor-ligand interaction can support distinct neuronal functions.