Regulation of meiotic central spindle function, homolog bi-orientation and co-orientation in Drosophila oocytes
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Das, Arunika.
Regulation of meiotic central spindle function, homolog bi-orientation and co-orientation in Drosophila oocytes. Retrieved from
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TitleRegulation of meiotic central spindle function, homolog bi-orientation and co-orientation in Drosophila oocytes
Date Created2016
Other Date2016-01 (degree)
Extent1 online resource (xv, 163 p. : ill.)
DescriptionIn the oocytes of many animals including humans, spindles are assembled in the absence of centrosomes. It is poorly understood what organizes the bipolar spindle in this system and directs attachment of chromosomes to opposing poles, a process known as bi-orientation. Previously it was shown that the kinesin 6 motor protein, Subito, is important for meiotic central spindle assembly and localization of the chromosomal passenger complex (CPC). I analyzed the role of different domains of Subito, to understand what restricts the activity of the motor to the chromatin, in meiosis. I found that the N-terminus of Subito, is required for localization of the kinesin to microtubules possibly in conjunction with the C-terminus. I also identified domains of Subito N-terminus that are required for mitosis, but may be dispensable for meiosis. I also analyzed mutants obtained from a synthetic lethal screen with Subito and found that the centralspindlin complex, is required for both homolog bi-orientation and Subito localization in meiosis. Surprisingly, I also found that downstream targets of this complex like Rho1 and Sticky (Citron kinase), are important for bi-orientation. In addition, another target from the screen, Polo kinase, which is a kinetochore protein is required for maintaining karyosome structure. Altogether, these results have given rise to a model where late cytokinesis proteins are involved in regulating central spindle assembly and directing bi-orientation possibly by modulating error correction by the kinase, Aurora B. It is unclear how the CPC function is regulated to establish tension between homologs and correct errors. Phosphatases have been shown to be important for a similar function in mitosis. However the role of phosphatases in meiosis was unknown. I have found that Drosophila PP1 is required for maintaining karyosome structure, peri-centromeric cohesion and co-orientation at metaphase I, in an Aurora B dependent manner. Kinetochore assembly by Aurora B, is also opposed by PP1. These results taken together provide insight on how Aurora B activity is balanced in meiosis, and emphasize the important role played by PP1 in oocytes.
NotePh.D.
NoteIncludes bibliographical references
Noteby Arunika Das
Genretheses, ETD doctoral
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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