Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

The exocyst complex is a conserved protein complex that tethers the secretory vesicles to the site of membrane fusion during exocytosis, an essential cellular process that transports molecules, such as protein, to the cell surface or extracellular space. We identified a small molecule that targets the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex to inhibit exocytosis. This compound made it possible to control the dynamics of the exocytosis process in a dosage-dependent manner in different organisms and overcame the mutant lethality and genetic redundancy issues in studying mechanisms of exocyst complex regulation. Further design of molecules with higher affinity and more potent activity may make it possible to use drugs to control human diseases related to exocytosis, such as cancer and diabetes.