Undergraduate Honors Thesis Projects

Date of Award

3-22-2018

Document Type

Honors Paper

Degree Name

Biochemistry and Molecular Biology-BS

Department

Biochemistry and Molecular Biology

Advisor

Dr. John T. Tansey

First Committee Member

Dr. Jeffery S. Lehman

Second Committee Member

Dr. Jonathan DeCoster

Keywords

Perilipin, Nucleus, Mitochondria, Lipid Metabolism

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Molecular Biology

Abstract

Perilipins are a family of five proteins found on the surface of lipid storage droplets in nearly all tissues. These proteins act as cofactors for lipases and scaffolding for other proteins involved in lipid metabolism. In addition to the lipid droplet surface, members of the perilipin family have been found in the cytosol, endoplasmic reticulum, plasma membrane and mitochondria. The localization of these proteins is in part due to the phosphorylation state of the perilipin in question. Many other biological processes occur through kinase pathways, which have numerous cellular outcomes. Recently, perilipin 5 has been shown to localize to the nucleus when phosphorylated by PKA on serine 155. In the nucleus, it interacts with the peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1α) to regulate gene expression. In silico analysis of a phosphomimetic mutant (Ser155Asp) indicates that this site is part of a potential nuclear localization sequence. Using a CHO model cell line, we observed that translocation to the nucleus could be stimulated by treatment with forskolin and isobutylmethylxanthine (IBMX) and occurred independently of oleic acid treatment to promote triacylglycerol deposition. This thesis aims to explore the nuclear transport mechanism of perilipin 5 through investigating other phosphorylation pathways and nuclear recognition motifs that affects the subcellular localization. These data have the potential to gain insights to the regulation of perilipin 5 trafficking into the nucleus, interactions with other proteins such as PGC-1a and regulation of processes such as mitochondrial biogenesis.

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