M. Iwig et al., GROWTH-REGULATION BY CELL-SHAPE ALTERATION AND ORGANIZATION OF THE CYTOSKELETON, European journal of cell biology, 67(2), 1995, pp. 145-157
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.