Vanden Broek, Kara et al. (2021) International Worm Meeting "RACK-1 is required for proper GLD-1 sub-cellular localization and function"

Wang, Chris, Vanden Broek, Kara, Hansen, Dave

[International Worm Meeting, 2021]

Stem 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 specialized cells or proliferate to maintain their population for future use. We are focusing on identifying the molecular mechanisms that regulate the proliferation/differentiation decision of stem cells using the C. elegans germ line as a model. C. elegans' germline stem cells (GSCs) proliferate to maintain the stem cell pool and differentiate to produce gametes. The conserved STAR family, RNA binding protein, GLD-1/Quaking, promotes differentiation and is required to maintain a proper balance between proliferation and differentiation. When gld-1 activity is lost, along with gld-2 activity, which functions redundantly with gld-1 to promote differentiation, a germline tumour of proliferating stem cells is formed. Previous research has shown that the pattern of GLD-1 germline accumulation is key to controlling its activity. We have found that GLD-1 subcellular localization is likely also involved in regulating GLD-1's activity. We identified rack-1 as a regulator of GLD-1 subcellular localization. rack-1 mutants have a severe disruption in GLD-1's subcellular localization; while wild-type GLD-1 is cytoplasmic, in rack-1 mutants GLD-1 localizes to germ granules. This disruption in localization appears to impact GLD-1's activity, as a loss of rack-1 phenocopies a reduction, or loss, of gld-1 activity in various genetic backgrounds. Our research is revealing a novel mechanism where the activity of GLD-1 is regulated by its subcellular localization. This provides an additional layer of regulation in the proliferation/differentiation decision of C. elegans GSCs.

Sangari, Sadaf et al. (2021) International Worm Meeting "Understanding the Role of Scaffold Protein Activated C Kinase 1 (RACK-1) in Germ Line Stem Cells of Caenorhabditis elegans"

Sangari, Sadaf, Vanden Broek, Kara, Hansen, Dave, Wang , Chris

[International Worm Meeting, 2021]

Stem cells are unspecialized cells that are able to proliferate to produce more stem cells (mitosis) or differentiate to produce specialized cells. The balance between proliferation and differentiation is controlled by highly regulated signaling pathway(s). The C. elegans germ line is a powerful model that allows genes and pathways that play a crucial role in establishing and maintaining this balance to be identified. The C. elegans gonad contains two gonad arms, where proliferating germline stem cells are located at the distal ends of each arm, while differentiating cells such as sperm and oocyte are located more proximally. The balance between proliferation and differentiation allows this spatial patterning to be maintained in the germline. Recently, our lab has identified the influence of the scaffold protein RACK-1, which is conserved between humans and C. elegans, on the proliferation vs. differentiation pathway. My research is investigating the role of this scaffold protein on maintaining the balance between proliferation and differentiation. A mutation that eliminates rack-1 results in lowering and mis-localization of the translational repressor protein GLD-1 (Germ Line Defective-1) in the differentiation pathway. Furthermore, loss of rack-1 results in lower brood size and sterility at higher temperatures. My research seeks to identify the mechanism (either direct or indirect) by which RACK-1 is impacting GLD-1 and furthermore, the differentiation and proliferation decision. My research will provide insight into how stem cell behaviour is regulated in the C. elegans germline.