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Growth regulation by cell shape alteration and organization of the cytoskeleton.

The correlation between cellular growth and microfilament-dependent morphology was investigated. It was found that the proliferative growth of various nontransformed cell lines does not only depend on cell adhesion to a suitable substratum and cell flattening but also on intact microfilaments. Disintegration of microfilaments by cytochalasin D (CD) as well as lactrunculin (LAT)-A and LAT-B is correlated with a strong decline of the number of DNA-synthesizing cells during a period of 8 to 12 h after application of the drug. RNA and protein synthesis are reduced already after a preincubation time of 2 h. Although microinjected rhodamine-phalloin is colocalized with microfilaments there is no stabilizing effect against CD even at high phaloidin concentrations. Microinjection of DNAse I results in a strong alteration of the microfilament system. The disorganization of microfilaments was correlated with a moderate decrease of protein synthesis 2 h after microinjection, whereas RNA synthesis remained unchanged, if RNase-free DNase I was used. The number of DNA-synthesizing cells was somewhat diminished 24 h after microinjection. Furthermore, the microfilament system is disorganized by microinjection of gelsolin and gelsolin segment 1 + 2, respectively. The severing the microfilaments by gelsolin is correlated with a significant restriction of RNA and protein synthesis during a period of 2 to 4 h after injection, but the labeling index remaining unchanged. Therefore, we assume that inhibition of the G0-G1-S transition is only caused by a disintegration of microfilaments lasting longer than 4 h. The significance of microfilament organization for growth regulation is discussed.