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.
Iwig
M
M
Institute of Physiological Chemistry, Faculty of Medicine, Martin Luther University, Halle (Saale)/Germany.
Czeslick
E
E
Müller
A
A
Gruner
M
M
Spindler
M
M
Glaesser
D
D
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D003850:Deoxyribonuclease I / Q000494:pharmacology; D004847:Epithelial Cells; D005347:Fibroblasts; D018260:Gelsolin / Q000494:pharmacology; D006801:Humans; D007399:Interphase / Q000187:drug effects; D018374:LLC-PK1 Cells; D008845:Microinjections; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013552:Swine; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000470:Alkaloids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018260:Gelsolin; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; C024287:phalloin; D012313:RNA; D004247:DNA; D003850:Deoxyribonuclease I; C037068:latrunculin B; C037067:latrunculin A