The sorting of proteins to lysosomes is studied because this is presently the best understood sorting process. Upon arrival in the Golgi complex, newly synthesized lysosomal enzymes acquire a mannose 6-phosphate (man6P) moiety that enables these enzymes to bind to man6P-specific receptors. The man6P receptor-enzyme complexes are then delivered by transport vesicles to an acidic prelysosome, where the enzymes are released; the man6P receptors then return to the Golgi complex for another round of transport. The biochemistry of this delivery process is being studied by reconstituting the vesicular transport of the man6P receptor from prelysosomes back to the Golgi complex in a cell free system. Now the project will define the molecular components that are used by the cell to form transport vesicles, target them to a specific destination, and enable them to fuse. Since almost nothing is known about the molecular components that facilitate intracellular transport, it may be possible to identify new proteins that mediate this vesicular transport process. To streamline operations, eukaryotic cells have devised a set of compartments that carry out specialized tasks, and therefore must be supplied with a unique set of proteins. The goal of this research is to understand, in molecular terms, how cells establish and maintain distinct membrane-bound compartments. This will lead to an understanding of the molecular mechanisms by which proteins are targetted to specific intracellular estinations.
