The Variation of STRIPAK Components in Regulating Katanin Microtubule-severing in the Caenorhabditis elegans Embryo

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dc.contributor.advisorMains, Paul
dc.contributor.authorLu, Tammy
dc.contributor.committeememberBrook, William
dc.contributor.committeememberTarailo-Graovac, Maja
dc.date2021-11
dc.date.accessioned2021-07-01T17:05:49Z
dc.date.available2021-07-01T17:05:49Z
dc.date.issued2021-06-29
dc.description.abstractMicrotubule-severing plays important roles in organism development, including for cell structure and cell division. Using C. elegans, I studied the regulation of katanin, a conserved microtubule-severing complex. Katanin is required for oocyte meiotic spindle formation; however, it must be inactivated for mitosis to proceed as continued katanin expression is lethal. In addition to two ubiquitin-based protein degradation pathways, another ubiquitin ligase, HECTD1 ubiquitin ligase homologue (HECD-1), regulates katanin activity without affecting katanin levels. Most regulators of katanin act as either a katanin activator or inhibitor; however, hecd-1 switches from being an activator in meiosis to an inhibitor in mitosis. My project set out to characterize the mechanism of hecd-1 mediated regulation of katanin. I used a CRISPR FLAG-tagged HECD-1 to compare the levels and localization of HECD-1 in meiosis and mitosis. HECD-1 showed ubiquitous expression in the cytoplasm throughout meiosis and early development and its levels remained unchanged. In other organisms, HECD-1 is a component of the striatin-interacting kinase phosphatase (STRIPAK) complex. This complex has been known to affect blood vessel formation, apoptosis, cell proliferation and a variety of signalling pathways. Using double mutants and genetic knockdowns, I found the STRIPAK complex components affected katanin activity differently. STRIPAK core components (farl-11, cash-1, let-92, gck-1), except for ccm-3, were katanin inhibitors in mitosis and activators in meiosis, much like hecd-1. In contrast, variable components (M4.1, otub-2) functioned as activators of katanin activity in meiosis and mitosis, while other components (mob-4, C49H3.6) were not involved in katanin microtubule-severing. These experiments outline separate functions for the STRIPAK complex and suggest a paradigm in which the addition of variable components alters the function of the complex. Additional experiments indicate that katanin may be involved with the central spindlin or a tubulin chaperone pathway. My research elucidated the interactions of nearly all the STRIPAK complex components in a single in vivo system and revealed their roles in katanin microtubule severing and cell division.en_US
dc.identifier.citationLu, T. (2021). The Variation of STRIPAK Components in Regulating Katanin Microtubule-severing in the Caenorhabditis elegans Embryo (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/38972
dc.identifier.urihttp://hdl.handle.net/1880/113574
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectC. elegansen_US
dc.subjectkataninen_US
dc.subjectmeiosisen_US
dc.subjectSTRIPAKen_US
dc.subjectdevelopmenten_US
dc.subjectmitosisen_US
dc.subjectmicrotubulesen_US
dc.subjectgeneticsen_US
dc.subjectHECD-1en_US
dc.subject.classificationEducation--Sciencesen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationGeneticsen_US
dc.subject.classificationPhysics--Molecularen_US
dc.titleThe Variation of STRIPAK Components in Regulating Katanin Microtubule-severing in the Caenorhabditis elegans Embryoen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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