RAB-10 cooperates with EHBP-1 to capture vesicular carriers during post-Golgi exocytic trafficking.

Post-Golgi exocytic trafficking, fundamental for secretion and cell surface component integration, remains incompletely understood at the molecular level. Here, we investigated this process using Caenorhabditis elegans and mammalian cell models, revealing a novel exocytic carrier capturing mechanism involving the small GTPase RAB-10/Rab10 and its effector EHBP-1/EHBP1. EHBP-1, localized in recycling endosomes, selectively captures RAB-10-positive lipoprotein exocytic carriers through its interaction with active RAB-10, thereby promoting the delivery of exocytic cargo to recycling endosomes. A detailed mechanistic examination demonstrated the synergy between EHBP-1's RAB-10-binding coiled-coil domain and its PI(4,5)P2-binding C2 domain in the capturing process. Of note, we identified LST-6/DENND5 as a specialized guanine nucleotide exchange factor (GEF) for RAB-10 in this particular pathway, distinct from the GEF involved in basolateral recycling. Following the RAB-10-EHBP-1-mediated capture, the exocyst complex carries out its function. Taken together, this study suggests a potential tethering mechanism for basolateral post-Golgi exocytic carriers, highlighting the coordination among membrane compartments in regulating this trafficking route.