A role for the sterol-binding protein Osh4/Kes1 in polarized growth

In the budding yeast Saccharomyces cerevisiae, seven OSBP-homologues (Osh) proteins are implicated in the transfer of sterol lipids between membranes within cells. To test whether Osh4p acts as a sterol transfer protein, a sterol-binding deficient mutant was analyzed. The mutant Osh4 protein was hyperactivated despite its inability to bind sterols, contrary to what is predicted for a sterol transporter. OSH genes also have an established role in vesicle docking during polarized exocytosis. To determine how Osh4p might affect vesicle docking, genetic interactions between OSH4, actomyosin-related genes, and regulatory genes involved in vesicle docking were analyzed. Genome-wide screens were performed to identify novel OSH genetic interactions and to better understand the functional interrelationship between the seven OSH genes. These results suggested that a primary role of the OSH genes is to regulate vesicle docking during polarized exocytosis, and not necessarily for the direct transfer of sterols between membranes.