Protein prenylation is an enzymatic, post-translational modification made to proteins containing a “CAAX” motif in which an isoprenoid unit of either 15 or 20 carbons is attached to the protein’s C-terminus. Protein prenylation has been implicated in a variety of diseases including cancer, viral infections, and neurodegenerative diseases. Previously, most Alzheimer’s disease (AD) studies have focused on neurons due to their susceptibility to form amyloid plaques and neurofibrillary tangles, biological hallmarks of AD. Recent evidence implicates microglial cells in the development of AD because of their role in neuroinflammation. This project seeks to understand the prenylation patterns of three types of brain cells: neurons, microglia, and astrocytes and the implications these patterns have for the development of AD. A metabolic labeling approach to proteomics was employed to map the prenylation patterns of the cell lines using a biorthogonal isoprenoid analog as a probe. A copper-catalyzed azide-alkyne reaction was performed to functionalize the probe with either a TAMRA fluorophore or a biotin handle for fluorescence and proteomics studies respectively. The fluorescence study showed differences between prenylation levels and prenylation patterns between the cell lines specifically in the area of analysis from 20-25 kD. The proteomics study showed a total of 32 prenylated proteins shared between astrocyte and microglial cell types. The microglial cell line was found to have 6 unique prenylated proteins while the astrocyte cell line was found to have 15 unique prenylated proteins. The neuron cell line offered inconclusive results due to high levels of background labeling and will be further explored in the future.

Protein prenylation and implications in Alzheimer’s disease

2019 Spring National Meeting

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