All cells are capable of sampling their environment through a process called endocytosis. Endocytosis is involved in diverse aspects of cellular physiology including modulating responses to growth factors, recycling at nerve terminals, catabolism of internalized nutrients, processing of antigens during immune reactions, and maintenance of cell polarity. Polarized epithelial cells have discrete apical and basolateral plasma membrane domains and can endocytose cellular membrane as well as extracellular fluid from either membrane domain. Upon internalization, the membrane and fluid cargo are transported to various intracellular compartments. We are interested in delineating these compartments, determining in which compartments different membrane components and fluid are sorted from one another, and analyzing the regulatory mechanisms that control membrane flow into and out of these compartments.

Our laboratory is also interested in bladder umbrella cells. These epithelial cells sit at the interface between urine and the underlying tissue and have an important barrier function. One little understood aspect of this barrier function is how umbrella cells adapt to the cycles of filling and voiding, and what role they play in the bladder's ability to accommodate large changes in urine volume. One of the goals of our research is to examine the hypothesis that the abundant discoidal vesicles that underlie the apical cell surface of umbrella cells fuse with the apical plasma membrane in response to stretch and thereby increase apical surface area. Upon voiding the membrane added during filling must be re-internalized. We are currently exploring the mechanisms that stimulate voiding-induced endocytosis and the pathways that couple exocytosis and endocytosis in these cells.

Current projects in the laboratory include:

I. Analysis of endocytic pathways in polarized MDCK cells

II. Regulation of endocytic traffic by Rho family GTPases

III. Stretch-regulated endocytosis/exocytosis in bladder uroepithelium