The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction of C. elegans

Abstract

Adhesion G protein-coupled receptors (aGPCR) are unique molecules. They are able to transmit classical signals via G-protein activation (7TM-dependent/cis signaling) as well as to mediate functions solely through their extracellular N termini, completely independent of the seven transmembrane helices domain (7TM) and the C terminus (7TM-independent/N terminus-only/trans function). This dual mode of action is highly unusual for GPCRs and allows for a plethora of possible cellular consequences. However, the physiological implications and molecular details of this N terminus-mediated signaling are not well understood. Here, we identify three distinct 7TM-independent/trans functions of the aGPCR Latrophilin homolog LAT-1 in the nematode Caenorhabditis elegans together regulating reproduction: sperm guidance, germline apoptosis and proliferative activity of germ cells in the gonadal stem cell niche. In these contexts, the receptor elicits its functions in a non-cell autonomous manner from adjacent somatic cells. These functions might be realized through alternative splicing of the receptor specifically generating N terminus-only variants. Thus, our findings shed light on the versatility of 7TM-independent/N terminus-only/trans functions of aGPCR and discusses possible molecular details.