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Cover  This month's cover shows intracellular membranes in a tissue culture cell (CV-1 monkey kidney epithelial cell) stained by a lipophilic fluorescent dye (Terasaki et al., 1984). The technique provides good preservation by means of glutaraldehyde fixation and by avoidance of detergent treatment. The nonspecific lipophilic dye stains mitochondria, lysosomes, and other organelles, with the most striking being the endoplasmic reticulum (ER).

The peripheral regions of cells in culture appear to be spread to a minimal thickness. The ER, which is three-dimensional elsewhere, is constrained to a single two-dimensional layer. This particular arrangement of the ER, which is similar to that in the whole mount electron micrographs by which the ER was discovered (Porter, 1953), makes certain characteristics of the ER more clear than in thin section electron micrographs. The basic structural elements are tubules and cisternae (large planar sheets). The tubules are usually joined at three-way junctions, and the whole system apparently forms a single continuous membrane, with an associated lumenal space, that extends throughout most of the cell. The cell-wide distribution appears to be due to an interaction with microtubules (Terasaki et al., 1986; Waterman-Storer et al., 1998), though the tendency to form networks is independent of the cytoskeleton (Dreier et al., 2000).

From cell fraction techniques, we know that the ER performs functions of protein synthesis, lipid synthesis, and calcium regulation; we also know that the ER has different domains, such as the nuclear envelope, or rough-versus-smooth ER. The ER thus resembles the plasma membrane in its singleness, multiple functions, and separate domains. In the plasma membrane, these characteristics are organized to perform integrated functions at the level of the whole cell; for instance, the neuronal plasma membrane has highly organized domains that serve the purposes of decision making, computation, and transmission of information. The ER seems likely to also have functions at the cellular level, but these functions are unknown due to the relative inaccessibility of the cytosol and the ER lumen, which makes it difficult to investigate the ER in its intact state at this time. Mark Terasaki.

	References:

• Dreier, L., and Rapoport, T.A. (2000). In vitro formation of the endoplasmic reticulum occurs independently of microtubules by a controlled fusion reaction. J. Cell Biol. 148, 883-898[Abstract/Full Text]
• Porter, K.R. (1953). Observations on a submicroscopic basophilic component of the cytoplasm. J. Exp. Med. 97, 727-750
• Terasaki, M., Chen, L.B., and Fujiwara, K. (1986). Microtubules and the endoplasmic reticulum are highly interdependent structures. J Cell Biol. 103, 1557-1568[Abstract]
• Teraskai, M., Song, J., Wong, J.R., Weiss, M. J., and Chen, L.B. (1984). Localization of endoplasmic reticulum in living and glutaraldehyde fixed cells with fluorescent dyes. Cell 38, 101-108[Medline]
• Waterman-Storer, C.M., and Salmon, E.D. (1998). Endoplasmic reticulum membrane tubules are distributed by microtubules in living cells using three distinct mechanisms. Curr. Biol. 8, 798-806[Medline]