The Role of Bik1p in Positioning the Mitotic Spindle in Yeast

University Of Rochester, Rochester NY

Investigators

Abstract

Correct positioning of the mitotic spindle is critically important for the development of all eukaryotes. This process utilizes both the actin and microtubule cytoskeletal systems. In the yeast, S. cerevisiae, spindle positioning requires two genetic systems, the Kar9p pathway and the dynein pathway. The Kar9p pathway functions prior to anaphase, whereas the dynein pathway functions later with the onset of anaphase. The molecular mechanisms that co-ordinate the two pathways are not known. Bik1p, a member of the CLIP 170 family of microtubule binding proteins, associates with proteins of both pathways and could therefore function to coordinate the activities of the two pathways. The goal of this research is to determine the function of interactions between Bik1p and proteins in the Kar9p pathway. These studies will use mutations that separate the interactions of BIK1 with proteins of the Kar9p pathway from the interactions of BIK1 with proteins in the dynein pathway. Several models will be tested for the role of the Bik1p-Kar9p pathway interactions. Because Bik1p is a plus-end microtubule-binding protein and interacts with Kar9p, the bik1 alleles will be tested for a role in Kar9p-dependent microtubule orientation. Bik1p will also be tested for a role in coordinating the temporal pattern of the Kar9p and dynein pathways using a series of biochemical and live-cell microscopy assays. A fuller understanding of how the two major pathways for spindle positioning are coordinated can provide important insights into how microtubules maintain semi-stable attachments while simultaneously undergoing shortening. This project will also promote the integration of education and research. The PI will provide summer training for undergraduates in the McNair program, which encourages low-income and minority students to pursue graduate education. The PI will further integrate teaching and research by forming an educational collaboration with SUNY-Genesco, a liberal arts college in the State University of New York system.