DIFFERENTIAL REGULATION OF ACTIN DEPOLYMERIZING FACTOR AND COFILIN INRESPONSE TO ALTERATIONS IN THE ACTIN MONOMER POOL

Myoblasts, transfected with a human gene encoding a beta-actin point m utation, down-regulate expression of actin depolymerizing factor (ADF) and its mRNA Regulation is posttranscriptional. Expression of cofilin , a structurally similar protein, and profilin, CapG, and tropomodulin is not altered with increasing mutant beta-actin expression. Myoblast s expressing either human gamma-actin or the mutant beta-actin down-re gulate the endogenous mouse actin genes to keep a constant level of ac tin mRNA,whereas the gamma-actin transfectants do not downregulate ADF . Thus, ADF expression is regulated differently from actin expression. The mutant beta-actin binds to ADF with about the same affinity as no rmal actin; however, it does not assemble into normal actin filaments. The decrease in ADF expression correlates with an increase in the una ssembled actin pool. When the actin monomer pool in untransfected myob lasts is increased 70% by treatment with latrunculin A, synthesis of A DF and actin are downregulated compared with cofilin and 19 other prot eins selected at random. Increasing the actin monomer pool also result s in nearly complete phosphorylation of both ADF and cofilin, Thus, AD F and cofilin are coordinately regulated by posttranslational modifica tion, but their expression is differentially regulated. Furthermore, e xpression of ADF is responsive to the utilization of actin by the cell .