ISOFORM-SPECIFIC COMPLEMENTATION OF THE YEAST SAC6 NULL MUTATION BY HUMAN FIMBRIN

The actin cytoskeleton is a fundamental component of eukaryotic cells, with both structural and motile roles. Actin and many of the actin-bi nding proteins found in different cell types are highly conserved, sho wing considerable similarity in both primary structure and biochemical properties. To make detailed comparisons between homologous proteins, it is necessary to know whether the various proteins are functionally , as well as structurally, conserved. Fimbrin is an example of a cytos keletal component that, as shown by sequence determinations and bioche mical characterizations, is conserved between organisms as diverse as Saccharomyces cerevisiae and humans. In this study, we examined whethe r the human homolog can substitute for the yeast protein in vivo. We r eport here that two isoforms of human fimbrin, also referred to as T- and L-plastin, can both substitute in vivo for yeast fimbrin, also kno wn as Sac6p, whereas a third isoform, I-fimbrin (or I-plastin), cannot . We demonstrate that the human T- and L-fimbrins, in addition to comp lementing the temperature-sensitive growth defect of the sac6 null mut ant, restore both normal cytoskeletal organization and cell shape to t he mutant cells. In addition, we show that human T- and L-fimbrins can complement a sporulation defect caused by the sac6 null mutation. The se findings indicate that there is a high degree of functional conserv ation in the cytoskeleton, even between organisms as diverse as S. cer evisiae and humans.