Arash Bashirullah

Progression through developmental transitions and maintenance of homeostatic physiology in adult organisms both require exquisite control of inter-organ communication. This communication is carried out by professional secretory cells, which are specialized for stimulus-dependent release of specific cargo proteins via regulated exocytosis. Given the central importance of this process, it is not surprising that defects in regulated exocytosis underlie many common and debilitating human diseases in neurons and in endocrine and exocrine organs. However, with the exception of the membrane fusion events that occur during cargo release, many cellular processes during regulated exocytosis remain poorly understood. Chemical mutagenesis screens in our lab looking for mutations that disrupt progression through development have revealed novel genetic regulators that are required for regulated exocytosis but function prior to cargo release. In these mutant strains, secretory cargo is produced but is not secreted, a phenotype highly reminiscent of defects observed in pancreatic ß-cells in type 2 diabetic patients. Collectively, these newly-identified genes outline previously uncharacterized cellular pathways that prepare secretory granules for exocytosis and will likely provide novel insights into the etiology of diabetes and other disorders that disrupt homeostatic control of metabolism.