Human BIN3 Complements the F-actin Localization Defects Caused by Loss of Hob3p, the Fission Yeast Homolog of Rvs161p

Abstract

The BAR adaptor proteins encoded by the RVS167 and RVS161 genes from Saccharomyces cerevisiae form a complex that regulates actin, endocytosis, and viability following starvation or osmotic stress. In this study, we identified a human homolog of RVS161, termed BIN3 (bridging integrator-3), and a Schizosaccharomyces pombe homolog of RVS161, termed hob3+ (homolog of Bin3). In human tissues, the BIN3 gene was expressed ubiquitously except for brain. S. pombe cells lacking Hob3p were often multinucleate and characterized by increased amounts of calcofluor-stained material and mislocalized F-actin. For example, while wild-type cells localized F-actin to cell ends during interphase, hob3Δ mutants had F-actin patches distributed randomly around the cell. In addition, medial F-actin rings were rarely found in hob3Δ mutants. Notably, in contrast to S. cerevisiae rvs161Δ mutants, hob3Δ mutants showed no measurable defects in endocytosis or response to osmotic stress, yet hob3+ complemented the osmosensitivity of a rvs161Δ mutant. BIN3 failed to rescue the osmosensitivity of rvs161Δ, but the actin localization defects of hob3Δ mutants were completely rescued by BIN3 and partially rescued by RVS161. These findings suggest that hob3+ and BIN3 regulate F-actin localization, like RVS161, but that other roles for this gene have diverged somewhat during evolution.