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Cover  Rapid movement of intracellular "particles" within animal and plant cells was observed by the light microscope dating back to its invention. The first molecular component involved in such movement was clearly identified by three laboratories in the mid-1980s as microtubules (Hayden, J.H., and Allen, R.D. [1984]. J. Cell Biol. 99, 1785-1793; Koonce, M.P., and Schliwa, M. [1985]. J. Cell Biol. 100, 322-326; Schnapp, B., et al. [1985]. Cell 40, 455-462). The experimental approach used by these three groups all involved a technically demanding strategy of combining video light microscopy (invented by S. Inoue and R. Allen only a few years earlier) with electron microscopy. In two studies, directed organelle transport was first visualized in living cells either along "linear elements" discerned by video microscopy (Hayden and Allen, 1984) or within extremely narrow cell processes (Koonce and Schliwa, 1985). Another study (Schnapp et al., 1985) visualized organelle transport along linear elements in squid axoplasm in vitro. Because the resolution of light microscopy is ~200 nm, these observations could not discern the molecular nature of the filament or reveal whether a single filament or bundle of cytoskeletal elements was involved. Resolving these issues required the electron microscopy. To accomplish this task in a convincing manner, all three laboratories first visualized organelle transport along a filament by video microscopy using a "marked" grid, fixed the preparation, and then found the exact same filament by electron microscopy. The cover (Figure 3 from Schnapp et al., 1985) shows a pair of "transport filaments" (at a ~150° angle) visualized first by video microscopy (left) and then by rapid freezing, rotary-shadowing electron microscopy (right) (smaller, nontransporting neurofilaments are indicated by arrows). The bottom image shows a higher-magnification view of the transport filament (corresponding to the box in the upper portion of the low-magnification image). The size and substructure of the transport filament seen in this and the other two studies revealed that it was a single microtubule. All three studies also reported the intriguing finding that bidirectional organelle transport occurred along single microtubules. Collectively, these studies set the stage for the reconstitution of organelle transport along purified microtubules and the identification of two opposite polarity motors (kinesin and cytoplasmic dynein) that powered bidirectional motion. Subsequent work indicated that organelle transport can occur along actin filaments as well (Kuznetsov, S.A., Langford, G.M., and Weiss, D.G. [1992]. Nature 356, 722-725). It is interesting to note that the above studies used very different cell types from the far reaches of the animal kingdom (corneal keratocytes from frog [Hayden and Allen, 1984], the giant freshwater ameba Reticulomyxa [Koonce and Schliwa, 1985], and the squid giant axon [Schnapp et al., 1985]). In this epoch in which biological studies are becoming compressed to a few model organisms with heavily sequenced genomes, these papers remind us of how cell biological insights can be made on "unusual" organisms that lack genetic tools but possess unique biological features.Ron Vale, Howard Hughes Medical Institute and Department of Pharmacology, University of California, San Francisco