Dissecting the Mitotic Golgi Membranes Mediated Microtubule Polymerization

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dc.contributor.advisorHenne, W. Mikeen
dc.contributor.committeeMemberGoodman, Joel M.en
dc.contributor.committeeMemberYu, Hongtaoen
dc.contributor.committeeMemberSeemann, Joachimen
dc.creatorGuo, Haijingen
dc.creator.orcid0000-0002-2908-9120
dc.date.accessioned2022-01-03T22:20:33Z
dc.date.available2022-01-03T22:20:33Z
dc.date.created2019-12
dc.date.issued2019-11-25
dc.date.submittedDecember 2019
dc.date.updated2022-01-03T22:20:34Z
dc.descriptionThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.en
dc.description.abstractA properly assembled astral microtubule network is required for correct mitotic spindle orientation, which is important in multiple development processes as it determines cell fate and function. The initiation and growth of astral microtubules was previously attributed to centrosomes and microtubule stabilizing proteins. Here in my dissertation research, I demonstrate that microtubules initiated by mitotic Golgi membranes contribute to the growth of astral microtubules and the proper orientation of the spindle. In turn, the microtubule initiation activity of mitotic Golgi membranes facilitates the proper inheritance of the single copy Golgi apparatus, which is essential in polarized cellular functions, including directional cell migration and secretion. Microtubule assembly is initiated by the Golgi resident protein GM130, which locally activates the spindle assembly factor TPX2 at the mitotic Golgi membranes. GM130 relieves TPX2 from inhibition by competing for importin α binding. The mitotic phosphorylation of importin α on Serine 62 by Cdk1 switches its substrate preference towards GM130 and enables the competition-based activation. The importin α S62A mutant impedes the local TPX2 activation and compromises the astral microtubules, which ultimately leads to misoriented spindles. Blocking of the GM130-importin α-TPX2 activation pathway reduces the astral microtubule growth rate. I also identified that the human GM130 homolog GLP harbors a domain that is highly similar to the TPX2 activating domain of GM130, which could potentially initiate microtubule assembly. My research reveals the novel role of mitotic Golgi membranes in astral spindle organization and the underlying mechanism that regulates this process in a spatio-temporal manner.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1290684161
dc.identifier.urihttps://hdl.handle.net/2152.5/9659
dc.language.isoenen
dc.subjectalpha Karyopherinsen
dc.subjectGolgi Apparatusen
dc.subjectMicrotubulesen
dc.subjectMitosisen
dc.titleDissecting the Mitotic Golgi Membranes Mediated Microtubule Polymerizationen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineIntegrative Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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UT Southwestern Graduate School of Biomedical Sciences