Polymerization of actin from the thymosin beta 4 complex initiated by the addition of actin nuclei, nuclei stabilizing agents or myosin S1.
Thymosin beta 4 forms a 1:1 complex with actin and thereby prevents polymerization. Rapid formation of filaments from this complex was observed, however, when actin trimers were added. Polymerization can likewise be initiated by the addition of one equivalent of phalloidin or, less effectively, cytochalasin B. Since both toxins, which reportedly support nucleation, have similar effects as the covalently linked actin trimers, it appears that the formation of filaments from the actin-thymosin beta 4 complex depends on the availability of stable actin nuclei. Remarkably, rapid polymerization was also observed if small amounts of myosin S1 were added, suggesting that also myosin, a protein functionally connected with polymeric actin, can serve as a nucleation center. Considering the existence of thymosin beta 4 and related peptides in numerous mammalian tissues, our data suggest that spontaneous formation of microfilaments in non-muscle cells may be regulated at the level of nucleation. Uncontrolled polymerization induced by the formation of phalloidin-stabilized nuclei may explain the acute toxic effects of phalloidin in hepatocytes.
Max-Planck-Institut für Medizinische Forschung, Heidelberg, Germany.
A
A
Reichert
D
D
Heintz
W
W
Voelter
M
M
Mihelic
H
H
Faulstich
D000199:Actins / Q000737:chemistry*; D003571:Cytochalasin B / Q000494:pharmacology; D005453:Fluorescence; D007700:Kinetics; D046911:Macromolecular Substances; D009132:Muscles / Q000737:chemistry; D015879:Myosin Subfragments / Q000494:pharmacology*; D010590:Phalloidine / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013947:Thymosin / Q000737:chemistry / Q000378:metabolism*; D014783:Viscosity; D000099201:Thymosin beta(4)
D000199:Actins; D003571:Cytochalasin B; D046911:Macromolecular Substances; D015879:Myosin Subfragments; D010590:Phalloidine; D011108:Polymers; D011189:Potassium Chloride; D013947:Thymosin; D000099201:Thymosin beta(4)