1997 Fleming Lecture, 139th meeting of the Society for General Microbiology, 7 January 1998: Protein targeting to the endoplasmic reticulum in yeast: Protein targeting to the endoplasmic reticulum in yeast

The eukaryotic cell is characterized by the presence of membrane-bound organelles that perform a variety of highly specialized functions. The structure and function of each organelle is largely defined by its unique complement of constituent proteins. Clearly, the bio- genesis and maintenance of these compartments demands that newly synthesized proteins must be accurately and efficiently targeted to their appropriate cellular location. Since most proteins begin their syn- thesis in the cytosol, their delivery to an organelle normally involves their translocation across at least one lipid bilayer. The selective translocation of large hydro- philic proteins across biological membranes is a complex process that is made all the more demanding by the need to maintain the integrity of the membrane so as to prevent the mixing of cytosolic and organellar contents. The endoplasmic reticulum (ER) plays a major role in intracellular protein trafficking. Proteins translocated into the ER can either remain resident there, or may be transported to the Golgi apparatus, the lysosomal network, or the cell surface. Transport from the ER occurs by vesicular budding and fusion, and so does not require cargo proteins to undergo any further membrane-translocation events. Protein translocation across the ER membrane is therefore fundamental to organelle biogenesis and protein secretion in eukaryotes. Here I propose to review some of the most important recent findings that have revolutionized our under- standing of this translocation mechanism.