Abstract. We have investigated accumulation of a-actinin, the principal cross-linker of actin filaments, in four Drosophila fliA mutants . A single gene is variably spliced to generate one nonmuscle and two muscle isoforms whose primary sequence differences are confined to a peptide spanning the actin binding domain and first central repeat . In fliA3 the synthesis of an adult muscle-specific isoform is blocked in flight and leg muscles, while in fliA4 the synthesis of nonmuscle and both muscle-specific isoforms is severely reduced . Affected muscles are weak or paralyzed, and, T HE cellular and developmental roles of the spectrin superfamily ofproteins are being clarified by genetics. Hemolytic diseases of humans are known to result from spectrin defects that weaken the erythrocyte plasma membrane, predisposing the cells to collapse in the face of circulatory system shear forces (Knowles et al., 1983 ;Marchesi et al., 1987) . Analyses of humans, dogs, and mice having muscular dystrophies have correlated dystrophin defects with syndromes of muscle wasting (Hoffman et al ., 1987;Cooper et al., 1988). These results suggest that mutant dystrophins engender muscle necrosis by failing to localize or anchor sarcolemmal glycoproteins (Ervasti et al., 1990) . Genetic investigations of the third spectrin superfamily member and principal actin filament cross-linking protein, a-actinin, have not been as informative. Gene knockout experiments performed in Dictyostelium did not confer a detectable phenotype (Wallraff et al., 1986;Noegel and Witke, 1988;Schleicher et al., 1988). This result almost certainly signifies that the role of a-actinin in nonmuscle cells is largely redundant, but does not clarify the function of the protein . aActinin mutations in Drosophila engender either lethal or flightless phenotypes (Fyrberg et al ., 1990) . No nonmuscle cell phenotypes have been noted, but within muscles disruptions of Z-discs and attachments of muscle fibers to epithelial tendon cells are readily apparent (Fyrberg et al., 1990).Our in the case of fliA3, atrophic. Their myofibrils, while structurally irregular, are remarkably normal considering that they are nearly devoid of a major contractile protein . Also surprising is that no obvious nonmuscle cell abnormalities can be discerned despite the fact that both the fliA'-andfliA4-associated mutations perturb the nonmuscle isoform . Our observations suggest that a-actinin stabilizes and anchors thin filament arrays, rather than orchestrating their assembly, and further imply that a-actinin function is redundant in both muscle and nonmuscle cells.Z-discs, where it has been proposed to cross-link ends of both parallel and antiparallel arrays of actin filaments (Suzuki et al., 1976;Endo and Masaki, 1982 ;Duhaiman and Bamburg, 1984; for review see Blanchard et al ., 1989) . In vitro studies have shown that at very low (0-4°C) temperatures, antiparallel dimers of a-actinin do indeed cross-link actin filaments (Goll et al ., 1972;Bennett et al., 1984), but the length of these cross-li...
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