J. David Castle
Primary AppointmentProfessor, Cell Biology
- BA, Biology, Carleton College, Northfield, MN
- PhD, Cell Biology, Rockefeller University, New York, NY
- Postdoc, Cell Biology, Yale Univ. Sch. of Med., New Haven, CT
- Postdoc, Biophysical Chemistry, Univ. of California, Berkeley, CA
Jordan Hall, 3-111
Charlottesville, VA 22908
Regulation of Membrane Recycling and Protein Secretion
We also maintain an interest in the function of Secretory Carrier Membrane Proteins (SCAMPs), a family of proteins that were discovered in my laboratory. Our work has been focused along two lines: 1) deciphering the complementary roles of SCAMPs 1 and 2 in exo-endocytic coupling during secretion by neuroendocrine cells including those derived from adrenal medulla and endocrine pancreatic islets; and 2) analysis of the function of SCAMP3 in regulating endocytic sorting of epidermal growth factor receptor (EGFR). Our most recent achievement regarding SCAMP1 is a demonstration that it is a key component controlling fusion pore closure and thereby determining the magnitude of export of stored hormone in response to cellular stimulation (Zhang and Castle, 2011). This regulatory role appears to involve an indirect coupling to the GTPase dynamin that mediates membrane scission. With respect to SCAMP3, we and our collaborators have recently shown that its levels govern the rate at which EGFR is degraded in response to EGF stimulation. SCAMP3?s role appears focused in sorting endosomes where it is able to interact with components of the ESCRT (Endosomal Sorting Complex Required for Transport) machinery that function in down regulation of growth factor receptors (Aoh et al, 2009; Falguieres et al, 2012). The particular role of SCAMP3 in supporting down regulation versus recycling of EGFR may be determined by its reversible ubiquitylation.
Finally, my laboratory contributes to a collaborative Program Project headed by Professor Lukas Tamm in the Department of Molecular Physiology and Biological Physics and Center for Membrane Biology. These studies are addressing structural dynamics of presynaptic membrane fusion.