Actin with Tumor-Related Mutation Is Antimorphic in Drosophila Muscle: Two Distinct Modes of Myofibrillar Disruption by

A mutant £-actin with an amino acid substitution from Gly-245 to Asp has been shown to be related to tumorigenic transformation of a human fibroblast cell line (Leavitt, J. et aL (1987) Mol. Cell Biol 7,2467-2476). To examine the effects of this mutation, we artificially introduced the same amino acid change into the Act88F actin gene of Drosophila melanogaster. The gene (Act88FGD24i) was inserted in the Drosophila genome to make transgenic adult flies which synthesize the mutant actin in the indirect flight muscles. The mutant actin was found to be antimorphic with regard to flight and also to cause myofibrillar disruption in transformants even in the presence of two normal alleles. It was initially incorporated into myofibrils and later induced their degeneration from center to periphery. This mode of myofibrillar disruption is distinct from that of previously reported Act88F mutations, where defects are found only in the peripheral region of myofibrils. This indicates that actin functions are altered differently in the two classes of antimorphic mutations. Actin is a multifunctional protein with a highly conserved amino acid sequence throughout phylogeny. To understan