GROWTH-REGULATION BY CELL-SHAPE ALTERATION AND ORGANIZATION OF THE CYTOSKELETON

The correlation between cellular growth and microfilament-dependent mo rphology was investigated. It was found that the proliferative growth of various nontransformed cell lines does not only depend on ceh adhes ion to a suitable substratum and cen flattening but also on intact mic rofilaments. Disintegration of microfilaments by cytochalasin D (CD) a s wed as latrunculin (LAT)-A and LAT-B is correlated with a strong dec line of the number of DNA-synthesizing cells during a period of 8 to 1 2 h after application of the drug. RNA and protein synthesis are reduc ed already after a preincubation time of 2 h. Although microinjected r hodamine-phalloin is colocalized with microfilaments there is no stabi lizing effect against CD even at high phalloidin concentrations. Micro injection of DNase I results in a strong alteration of the microfilame nt system. The disorganization of microfilaments was correlated with a moderate decrease of protein synthesis 2 h after microinjection, wher eas RNA synthesis remained unchanged, if RNase-free DNase I was used. The number of DNA-synthesizing cells was somewhat diminished 24 h afte r microinjection. Furthermore, the microfilament system is disorganize d by microinjection of gelsolin and gelsolin segment 1 + 2, respective ly. The severing of microfilaments by gelsolin is correlated with a si gnificant restriction of RNA and protein synthesis during a period of 2 to 4 h after injection, but the labeling index remained unchanged. T herefore, we assume that inhibition of the G(0)-G(1)-S transition is o nly caused by a disintegration of microfilaments lasting longer than 4 h. The significance of microfilament organization for growth regulati on is discussed.