Date of Graduation

5-2017

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor

Michael Lehmann

Committee Member

Timothy Evans

Second Committee Member

Fiona Goggin

Keywords

Drosophila, Lipin, Metabolism

Abstract

Lipins are a family of proteins that have critical functions in the control of fat storage and energy homeostasis. Biochemically, lipins have two functions. They provide an enzymatic activity (phosphatidate phosphatase or PAP activity) in the glycerol-3 phosphate pathway that leads to the production of storage fats (triacylglycerols). In addition, they play a role in the regulation of genes in the cell nucleus as transcriptional co-regulators. The PAP activity of lipins has been widely studied in a number of organisms. However, the transcriptional co-regulator function is not as well described in the literature. The transcriptional function of lipins depends on its nuclear translocation caused by the presence of a nuclear localization signal (NLS) in the protein. Data from our lab have shown that expression of Lipin protein lacking the NLS (LipinΔNLS) from a transgene leads to a disruption of timely development of Drosophila melanogaster. This suggests that Lipin has nuclear roles in the control of development.

The overarching goal of this project was to further examine nuclear roles of Lipin in Drosophila melanogaster. LipinΔNLS mutant was generated by CRISPR/Cas9 mutagenesis. Phenotypic and genetic analyses of the LipinΔNLS mutant indicate that nuclear functions of Lipin are essential for animal survival. LipinΔNLS and LipinΔPAP mutants complement each other restoring enzymatic and nuclear functions in these transheterozygous animals. Generation of a LipinΔNLS mutant provides a variety of future directions that can be pursued by our laboratory.

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