Regulation of the localization of Lte1, a S. cerevisiae mitotic exit activator

Abstract

The regulation of eukaryotic cell division, which involves the faithful segregation of a complete DNA complement to each daughter cell, is a fundamental area of research in biology. Entry into mitosis is initiated by the action of mitotic cyclins complexed with the cyclin dependent kinase (CDK). Once the chromosomes have been successfully segregated, the exit from mitosis ensues. In order for cells to exit from mitosis, mitotic CDKs must be inactivated. The inactivation of mitotic CDKs, in turn, promotes cytokinesis. In S. cerevisiae, mitotic exit is controlled by the Mitotic Exit Network (MEN). In this simple eukaryote, the tight coupling of nuclear migration and mitotic exit is achieved in part by the spatial segregation of Lte1, a positive activator of the MEN, and Teml, a GTPase that acts at the top of the MEN signaling cascade. The spatial segregation of Lte1 and Teml is particularly important in cells with mispositioned anaphase spindles, and plays a role in the prevention of aneuploidy. A model for the regulation of Lte1 localization across the cell cycle is proposed. Additionally, the role of Lte1 localization in mediating its ability to promote mitotic exit is examined. This work identifies novel connections between polarity determinants, Ras signaling, and mitotic exit.