A conservative mechanism of polarization drives hyphal growth in the opportunistic yeast pathogen Candida albicans
2014-08
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
A conservative mechanism of polarization drives hyphal growth in the opportunistic yeast pathogen Candida albicans
Authors
Published Date
2014-08
Publisher
Type
Thesis or Dissertation
Abstract
In eukaryotes, different cell morphologies are generated by fine-tuning the spatiotemporal regulation of the polarized growth machinery. Studying hyphal growth in the multimorphic opportunistic yeast pathogen Candida albicans provides a unique opportunity to understand how highly polarized cell structures are generated and maintained, and has the potential to provide insight into mechanisms of pathogenesis. Hyphal cell morphology requires that polarized growth machinery be held at hyphal tips over extreme distances and through multiple cell cycles. Deletion of the bud-site selection GTPase Rsr1 in C. albicans results in defects in cell size and shape not observed in studies of its ortholog in the related yeast Saccharomyces cerevisiae. This suggests that, in addition to its role in bud site selection, Rsr1 has expanded function in C. albicans, which impacts polarized growth and the generation of the hyphal morphology. Here, I show that loss of Rsr1 results in changes to a hyphal-specific tip structure, the Spitzenkörper, a downstream developmental indicator of Cdc42 signaling, and key regulator of polarized growth. Also, my results show that Rsr1's function impacts the spatiotemporal distribution of Bem1 a marker of the active form of Cdc42. Interestingly, the changes in the distribution of Cdc42 activity are also correlated with reduced expression of the hyphal transcriptional program. In addition, I also show the differential effects of the guanine nucleotide binding states of Rsr1, through the manipulation of the Rsr1 GAP, Bud2, and GEF, Bud5. Through the action of Bud2, Rsr1-GDP acts as a global inhibitor that limits competitive, stochastically-activated clusters of Cdc42, and also as a lateral inhibitor of growth at hyphal tips that strongly influences the overall width of the hypha. In contrast, Rsr1-GTP, through Bud5 activity, is needed to efficiently nucleate single clusters of Cdc42 activity during hyphal emergence, and also contributes to the extremely narrow morphology of the hypha. Altogether, the data presented here suggest that Rsr1 cycling supports a conservative mechanism of polarization that optimizes the efficiency with which polarization occurs, which is required for the maintenance of polarized growth.
Description
University of Minnesota Ph.D. dissertation. August 2014. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisors: Dr. Cheryl Gale and Dr. Judith Berman. 1 computer file (PDF) ; ix, 117 pages, appendix A.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Pulver, Rebecca. (2014). A conservative mechanism of polarization drives hyphal growth in the opportunistic yeast pathogen Candida albicans. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/167427.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.