Green, Samuel A.
Associate Professor, Cell Biology
PO Box 800732
Molecular Mechanisms of Receptor-Sorting in Endosomes; Identification and Characterization of Neuroendocrine Secretory Granule Membrane Proteins
Specific functions of the many different membrane-bounded organelles in eukaryotic cells rely on their characteristic protein compositions. A key feature in the biogenesis and maintenance of these organelles is the correct sorting of proteins, mediated by structural information that is independent of the biochemical activity of the protein. Our goals are to elucidate the trafficking pathways followed by specific organellar membrane proteins, and to understand the molecular mechanisms that drive selective sorting events in these pathways. In particular, we are interested in the mechanisms of assembly and recycling of regulated secretory granule membranes in neuroendocrine cells. We are using molecular, immunological and cell biological approaches to study protein sorting in the secretory and endocytic pathways.
P-selectin is also being studied as a marker of the secretory granule membrane in transfected neuroendocrine cells, in which very few endogenous markers have been identified. We have recently found that granule targeting of P-selectin is defective in mice harboring mutations in the AP-3 adaptor sorting complex. This is the first clue to the identity of the sorting machinery necessary for granule membrane assembly. The role of AP-3 adaptor and other proteins in granule membrane assembly is currently being studied using transfected neuroendocrine cell lines as well as endocrine tissue from mutant mouse strains. The long term goal is to extend these studies to assembly and regulation of secretory granules in neurons, about which we currently know virtually nothing beyond the identity of their soluble content proteins.