The main interests the Castle lab are in mechanisms of membrane trafficking invovled in cell secretion and endocytosis. We are using molecular and cell biological approaches to study the pathways of protein secretion in regulated secretory cells and to explore the function of specific membrane proteins in exocytosis and internalization and recycling of cell surface proteins.

Our studies are focused on two families of proteins -- one discovered by us called SCAMPs (for Secetory Carrier Membranes Proteins) and the other SNAPs 23, 25 which are members of the family of SNARE proteins that regulate membrane fusion at the cell surface. SCAMPs are evolutionarily conserved, and we have now identified mammalian isoforms in most membranes that function in intracellular membrane trafficking. Work in progress suggests that selected SCAMPs may function at a late step in exocytosis as studied in mast cells and exocrine acinar cells while other SCAMPs appear to interact with the Epidermal Growth Factor Receptor following ligand binding in fibroblasts and may contribute to its interalization and down regulation. Studies of SNAP23 in mast cells have shown that its stimulus-dependent relocation from the cell surface to secretion granules is essential to signalling and expediting compound exocytosis. Recentrly, we have begun to use Drosphila as a genetic system for analyzing the fuctions and interactions of these proteins during development and in specific tissues. While the majority of our studies are focused on understanding the roles of these proteins in the physiological control of membrane and molecular trafficking, they serve as a basis for future conserations of dysregulation of secretion and membrane and molecular trafficking that are relevant to various diseases inlcuding cystic fibrosis, cancer, and to the acute allergic response.

 



Designed by Ammar Sarraf & Sharmil Shah | January 9th 2004 | aas6w@virginia.edu