Actin in locomotion

y 1970, several ultrastructural studies reported that different cell types contained thin filaments, 50 Å in diameter, which resembled the actin filaments seen in muscle cells. Similar filaments were also observed in the growing tips of axons, where they formed a network or mesh along the periphery. By analogy, most scientists assumed these actin-like filaments would also be involved in contraction and promote cellular move-B ment. A series of papers published by Norman Wessells and his group Spooner et al., 1971) provided the necessary correlative link: only when there was filament structure was there also motile function. The studies were made possible by a new pharmacological tool. Cytochalasin B had been shown to inhibit motility (Carter, 1967), but without any real idea of mechanism. Schroeder (1969) then demonstrated that the drug also inhibited cytokinesis—a process that, like the action of muscle, was thought to be con-tractile—and he correlated this action with the disruption of the 50-Å filament networks in cells. Wessells's group found a similar correlation between drug action and lack of filaments for cytochalasin B's inhibition of cell shape morphogenesis (Spooner and Wessells, 1970), and decided to see if the same held up when the drug was applied during neuron out-growth and cell locomotion. " The lab was unusual in encouraging graduate students to wander off into unrelated projects, " says Ken Yamada, then a student with Wessells and now at the NIH (Bethesda, MD). " So it was fascinating that everything fell together when we tested cyto-chalasin on the various systems. " First the group added the drug to neurons in culture, which caused the axons' growing tips, or growth cones, to round up. The drug disrupted the filamentous networks in the growth cones and halted axon elongation (Yamada et al., 1970; Yamada et al., 1971). In a parallel study, the group described a network of micro-filaments—similar in organization to the one found in growth cones—at the very leading edges of migratory glial cells. Cytochalasin B rapidly disrupted this network and halted cell migration (Spooner et al., 1971). When the drug was washed away in either system, the microfilament networks recovered and axon outgrowth or locomotion resumed. studies demonstrated that the filaments could bind heavy meromyosin (Spooner et al., 1973) and again when actin antibodies became available (Spooner and Holladay, 1981). " In our original papers, we intentionally avoided using the word actin, " says Yamada. How actin …