Control of secretory granule maturation by the pgant9 gene

2018

Challenge

Regulated secretion is an essential cellular process in which molecules are packaged into tiny particles called secretory granules. Secretory granules are unique cellular structures that store neuropeptides and hormones and transport them to the cell surface in a specific manner. Defects in this process are implicated in a variety of diseases, such as cystic fibrosis and inflammatory bowel disorders, but the exact factors involved have been poorly understood.

Advance

IRP researchers, led by Kelly G. Ten Hagen, Ph.D., used the fruit fly salivary gland as a model system for observing the development of secretory granules. Through this research, the team discovered that the pgant9 gene affects granule structure by producing an enzyme that transfers sugar molecules to other proteins when pgant9 is modified in a tissue-specific manner. In addition, the group discovered crystal structures associated with different modifications to pgant9 and identified a novel mechanism by which the enzyme’s specificity is achieved.

Impact

Understanding how the enzyme encoded by pgant9 and other, similar enzymes affect the process of secretory granule development will aid the development of strategies to treat diseases caused by the disruption of the secretory process.

Publications

Ji S, Samara N, Revoredo L, Zhang L, Tran DT, Muirhead K, Tabak LA, Ten Hagen KG. (2018). A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nature Commun. 9(1):3508. doi: 10.1038/s41467-018-05978-9.