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Cover  Cytoplasm is crowded! Cytoplasm was once seen as clear, viscuous fluid in which membraneous organelles, chromosomes, and the nucleus were suspended. Thin-section and whole-mount electron microscopy revealed the existence of the major cytoskeletal polymers, microtubules, actin filaments, and intermediate filaments. But it was a surprise to see the full extent to which the cytoplasm is occupied by structural proteins, as revealed by images such as this one from Hirokawa (1982, J. Cell Biol. 94: 129-142), or by related techniques (Schnapp and Reese, 1982, J. Cell Biol. 92: 667-679; Ellisman and Porter, 1980, J. Cell Biol. 87: 464-479). This view was obtained by fast-freezing saponin-extracted frog nerve, deep-etching to remove the ice, and metal-shadowing. The axon shown is so full of filamentous material that it is difficult to imagine how membraneous organelles, such as the mitochondria in this image, could move about, as they do continually and bidirectionally in the living cell. Presumably, the bridges linking microtubules with each other and with other structures must yield to accommodate the moving organelles. The identities of the major microtubule-associated bridges are known (e.g., MAP 1, MAP 2, tau), as are those of the neurofilament-associated extensions (NFL, NFM). Which of the bridges in this image are microtubule motor proteins and other linkers is uncertain. Reproduced from the Journal of Cell Biology, 1982, 94, 129-142, by copyright permission of the Rockefeller University Press.Richard B. Vallee