Investigating the role of RACK-1 in the C. elegans germ line
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AbstractStem cells are central to the development of multi-cellular organisms, including C. elegans and humans. Key to their function is their ability to differentiate into more specialized cells or proliferate to maintain their population for future use. Germline stem cells (GSCs) are a class of stem cells that are crucial for an organism’s reproductive success. GSCs proliferate to maintain the stem cell pool (self-renew) and differentiate to produce gametes (sperm/oocytes). A balance between proliferation and differentiation is necessary for proper germline function and the production of offspring throughout an organism’s life. This thesis uses the C. elegans hermaphrodite germline as an in vivo model to investigate the molecular mechanisms that regulate the proliferation/differentiation balance. In this thesis I have characterized RACK-1 as a modulator of the stem cell proliferation/differentiation balance. I found that RACK-1 is required for the proper activity of the conserved STAR family, RNA-binding protein, GLD-1/Quaking. GLD-1 is expressed throughout the cytoplasm in wildtype germlines, whereas in the absence of rack-1, GLD-1 levels are reduced, and GLD-1 becomes mislocalized to perinuclear aggregates (germ granules). This leads to a decrease, but not a complete loss, of GLD-1 activity. Specifically, a loss of rack-1 in combination with a loss of GLD-2 pathway function results in an over-proliferation phenotype. This phenocopies a partial reduction of gld-1 (gld-1(het)), but not a complete loss of gld-1, in the same genetic background. Additionally, loss of rack-1 rescues the proliferation defects in an fbf-1(0) fbf-2(0) mutant background similar to a reduction of gld-1 (gld-1(het)). Loss of rack-1 enhances the defective progression through meiosis phenotype associated with reduced GLD-1 activity. This data supports the model that rack-1 functions to modulate GLD-1 activity through controlling GLD-1’s subcellular localization and levels, thereby maintaining the proper proliferation/differentiation balance. This thesis reveals a novel mechanism that fine-tunes the activity of a key meiotic protein, GLD-1, to provide an additional layer of regulation in the proliferation/differentiation balance in the C. elegans germline
CitationVanden Broek, K. D. (2021). Investigating the role of RACK-1 in the C. elegans germ line (Unpublished doctoral thesis). University of Calgary, Calgary, AB.
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