[Endoplasmic reticulum: anatomy of a biologic membrane]

Endoplasmic reticulum (ER) is a large membranous network containing a wide variety of lipid and protein constituents which play important roles in cellular physiology. In this review, selection of experimental results are presented which have shaped our concepts of the molecular organization of ER. The morphological approach--electron microscope examination of ultra-thin sections of a variety of cells--led to the dualistic distinction between rough ER and smooth ER. Consequently, various attempts were made to separate the 2 entities and to demonstrate that they are endowed with distinct functional properties. Studies on the biogenesis of ER showed that enzymes associated with this organelle turn over independently, which was interpreted in terms of ER being biochemically organized as a mosaic. The results of isopycnic centrifugation of rat liver microsomes led us to conclude that the ER is comprised of three biochemically distinct domains and that the distribution of integral proteins in the lateral plane of the membrane (lateral topography) is primarily determined by their transmembrane disposition. Data on the transverse topography and the mode of biogenesis of ER enzymes are confronted with the predictions of this model.