Microfilaments in Cellular and Developmental Processes

Abstract

In our opinion, all of the phenomena that are inhibited by cytochalasin can be thought of as resulting from contractile activity of cellular organelles. Smooth muscle contraction, clot retraction, beat of heart cells, and shortening of the tadpole tail are all cases in which no argument of substance for alternative causes can be offered. The morphogenetic processes in epithelia, contractile ring function during cytokinesis, migration of cells on a substratum, and streaming in plant cells can be explained most simply on the basis of contractility being the causal event in each process. The many similarities between the latter cases and the former ones in which contraction is certain argue for that conclusion. For instance, platelets probably contract, possess a microfilament network, and behave like undulating membrane organelles. Migrating cells possess undulating membranes and contain a similar network. It is very likely, therefore, that their network is also contractile. In all of the cases that have been examined so far, microfilaments of some type are observed in the cells; furthermore, those filaments are at points where contractility could cause the respective phenomenon. The correlations from the cytochalasin experiments greatly strengthen the case; microfilaments are present in control and "recovered" cells and respective biological phenomena take place in such cells; microfilaments are absent or altered in treated cells and the phenomena do not occur. The evidence seems overwhelming that microfilaments are the contractile machinery of nonmuscle cells. The argument is further strengthened if we reconsider the list of processes insensitive to cytochalasin (Table 2). Microtubules and their sidearms, plasma membrane, or synthetic machinery of cells are presumed to be responsible for such processes, and colchicine, membrane-active drugs, or inhibitors of protein synthesis are effective at inhibiting the respective phenomena. These chemical agents would not necessarily be expected to affect contractile apparatuses over short periods of time, they either do not or only secondarily interfere with the processes sensitive to cytochalasin (Table 1). It is particularly noteworthy in this context that microtubules are classed as being insensitive to cytochalasin and so are not considered as members of the "contractile microfilament" family. The overall conclusion is that a broad spectrum of cellular and developmental processes are caused by contractile apparatuses that have at least the common feature of being sensitive to cytochalasin. Schroeder's important insight (3) has, then, led to the use of cytochalasin as a diagnostic tool for such contracile activity: the prediction is that sensitivity to the drug implies presence of some type of contractile microfilament system. Only further work will define the limits of confidence to be placed upon such diagnoses. The basis of contraction in microfilament systems is still hypothetical. Contraction of glycerol-extracted cells in response to adenosine triphosphate (53), ex...

Changes in microfilament organization and surface topogrophy upon transformation of chick embryo fibroblasts with Rous sarcoma virus.

“…12) and are associated with the plasma membrane (13,14,27). In untransformed nonmuscle cells, actin-containing microfilaments have been implicated in a number of cellular functions such as cytokinesis, endocytosis and exocytosis, cell adhesion to a substratum, cell locomotion, membrane ruffling, and maintenance of cell shape (7,(27)(28)(29)(30)(31).…”

Involvement of extracellular matrix in the formation of the inner ear

“…The forces which control the cellular shape changes that occur during this process are not understood. In a number of organs, folding is an active process, presumably generated by an actin-myosin interaction, that changes cell shape by changing cytoskeletal organization (e.g., Wessells et al, 1971;Schroeder, 1973). In a few cases, forces external to epithelial primordia have been implicated in causing morphogenesis, such as deposition of extracellular matrix in elevation of neural folds (Schoenwolf and Fisher, 19831, differentiation of somites (Solursh et al, 19791, and branching of the salivary gland (Nakanishi et al, 1986).…”

Cytochalasin B: Effects on Cell Morphology, Cell Adhesion, and Mucopolysaccharide Synthesis

“…Since cytochalasin B blocked tail resorption in ascidian tadpoles (9,10), an activity also attributed to microfilaments, this added further support to the notion that the antibiotic interfered with a "primitive contractile" system of microfilaments present in virtually all cells. Wessels and coworkers (11)(12)(13)(14) have elaborated on this theme and presented electron microscopic observations to the effect that alterations of cortical microfilaments induced by cytochalasin B not only interfered with cell motility, but with blood clotting, cytoplasmic streaming, and embryonic morphogenesis. The site of action of cytochalasin B in the cell is not known.…”