Nuclear architecture in budding yeast

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Nuclear architecture and nuclear function appear to go hand in hand, as defects in nuclear organization are associated with aging and diseases such as cancer. Moreover, certain cell types, such as neutrophils, have an irregular nuclear shape that is important for their function. We have been using budding yeast as a model system to study nuclear architecture. The yeast nucleus differs from that of higher eukaryotes in two regards: (1) yeast lack lamins, proteins that play a major structural role in shaping the nucleus in metazoans, and (2) the yeast nuclear envelope (NE) remains intact throughout the cell cycle, unlike the NE of higher eukaryotes, which breaks down during mitosis and reassembles after chromosome segregation is completed. Nonetheless, the yeast nucleus shares important features with nuclei of higher eukaryotes: the NE has to expand during the course of the cells cycle, during vegetative growth the nucleus maintains a spherical shape, with a volume that is proportional to cell volume, and during a mitotic arrest or in response to mating pheromone nuclear shape becomes irregular. How the NE expands and what determine nuclear size and shape are questions that remain to be resolved in all systems. To gain a better understanding of how nuclear envelope expansion is regulated, we are currently examining conditions, mutations and developmental states that affect nuclear expansion. One such state is exposure to mating pheromone, which causes the nucleus to elongate and the nuclear envelope to expand predominantly in the region adjacent to the nucleolus, much like in a mitotic delay. Using this system, we are investigating whether this expansion depends on phospholipid synthesis, and what signals are generated leading to nuclear shape change. This process is dependent on the Ste12 transcription factors. Therefore, to identify proteins and processes that could contribute to nuclear shape change, we examined the transcription profile of wild type and ste12 mutant cells treated with pheromone, and tested a number of candidate genes thta are induced in a Ste12-dependent manner for their role in nuclear envelope expansion. Ultimately, we want to examine whether principles that apply to nuclear envelope expansion upon exposure to pheromone also apply to mitosis nuclear envelope expansion.