SYNTHETIC-LETHAL INTERACTIONS IDENTIFY 2 NOVEL GENES, SLA1 AND SLA2, THAT CONTROL MEMBRANE CYTOSKELETON ASSEMBLY IN SACCHAROMYCES-CEREVISIAE

Abp1p is a yeast cortical actin-binding protein that contains an SH3 d omain similar to those found in signal transduction proteins that func tion at the membrane/cytoskeleton interface. Although no detectable ph enotypes are associated with a disruption allele of ABP1, mutations th at create a requirement for this protein have now been isolated in the previously identified gene SAC6 and in two new genes, SLA1 and SLA2. The SAC6 gene encodes yeast fimbrin, an actin filament-bundling protei n. Null mutations in SLA1 and SLA2 cause temperature-sensitive growth defects. Sla1p contains three SH3 domains and is essential for the pro per formation of the cortical actin cytoskeleton. The COOH terminus of Sla2p contains a 200 amino acid region with homology to the COOH term inus of talin, a membrane cytoskeletal protein which is a component of fibroblast focal adhesions. Sla2p is required for cellular morphogene sis and polarization of the cortical cytoskeleton. In addition, synthe tic-lethal interactions were observed for double-mutants containing nu ll alleles of SLA2 and SAC6 In total, the mutant phenotypes, sequences , and genetic interactions indicate that we have identified novel prot eins that cooperate to control the dynamic cytoskeletal rearrangements that are required for the development of cell polarity in budding yea st.