Nuclear Migration and Spindle Positioning in Saccharomyces cerevisiae

During the last stages of cell division (mitosis), a structure within the cell, called the mitotic spindle, segregates each duplicated pair of chromosomes to opposite poles of the cell. In most organisms, cell division occurs perpendicular to the spindle at its midpoint between the separated chromosomes, ensuring that both cells receive a full complement of chromosomes. Many types of cells position their spindles to control the position and orientation of the division plane. This strategy is used during embryonic development to partition asymmetrically localized cell differentiation factors into one or the other of the daughter cells (spindle orientation). Spindle position and orientation also determines the architecture of many tissues. Generally, spindle movements are accomplished through interactions between the cortex of the cell and astral microtubules emanating from the ends of the spindle. However, the mechanisms for force production and the signals that coordinate the completion of mitosis with cytokinesis are not well understood.

In budding yeasts, such as Saccharomyces cerevisiae, cell division occurs at the mother-bud neck. Therefore, budding yeast must move the spindle into the neck before dividing. Yeast has two partially redundant mechanisms to move the spindle into the neck. Before mitosis, the nucleus is dragged to the neck and oriented along the mother-bud axis when the ends of cytoplasmic microtubules are captured at the bud cortex by a protein called Kar9p. During mitosis spindle movement into the neck is mostly accomplished by dynein-dependent sliding of microtubule sides along the bud cortex . Kar9p-dependent microtubule interactions with the bud cortex continue during mitosis and can serve as a backup mechanism for spindle movement into the neck by helping to orient and pull on the spindle as it elongates through the neck All of these nuclear and spindle movements require cytoplasmic microtubules to pass through the neck and interact with the bud cortex.

In cells lacking functional dynein or dynactin, spindle movement into the neck can be delayed. When this happens, cytoplasmic microtubules passing through the neck continue to probe the bud cortex and grow longer, often pushing the spindle further from the neck. When spindle movement into the neck is delayed, cytokinesis and mitotic exit is also delayed by a spindle position checkpoint.

Microtubule interactions with the cell cortex and cytoplasmic dynein are also important for nuclear and spindle positioning in Aspergillis nidulans and in higher organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mammals, including brain tissue mophogenesis in humans (Lissencephaly). However, the mechanisms by which the movements occur and the proteins involved in these movements are not nearly as well-defined as in fungi such as yeast.