This dissertation comprises work conducted on two distinct projects. The first project addresses the process of mammalian cell cytokinesis, a sequence of events near the end of mitosis that separates the contents of a dividing cell into two daughter cells. During cytokinesis, a cellular structure known as the midbody forms between the two sets of anaphase chromosomes and coordinates chromosome separation, membrane trafficking, and microtubule disassembly to ensure proper abscission. Although the midbody was first observed over a hundred years ago, hundreds of proteins are required for its function in abscission, and many molecular details of this process remain to be understood. Chapter II and III present evidence that at least two subunits of the nuclear histone H3 lysine 4 methyltransferase (H3K4MT) complex, WDR5 and MLL3, unexpectedly reside at the midbody, associate with several midbody proteins, and regulate cytokinesis. WDR5 localization at the midbody, but not the nucleus, requires the integrity of its central arginine-binding cavity, and several truncations of WDR5 exhibit selective enrichment at the midbody, but not within the nucleus. Additionally, two novel WDR5 and MLL3 associated proteins, KIF2A and SAF-A, respectively, are identified. These data represent the first known involvement of a nuclear H3K4MT subunit in abscission.

The second project (Chapter IV) implicates the mammalian target of rapamycin (mTOR) as a key player in the expression of reward-related behavior in a mouse model of substance abuse. Systemic administration of the mTOR inhibitor rapamycin greatly reduces mTOR activity in two addiction-related brain regions, the prefrontal cortex and dorsal striatum. Furthermore, while rapamycin has little effect on the learning of a conditioned place preference, it attenuates the expression of this preference during exposure to drug cues, and also blocks psychostimulant-induced locomotor sensitization after a period of drug withdrawal. Taken together, these data support the hypothesis that mTOR regulates the expression of reward behavior upon reactivation of a memory by environmental cues.