Authors

Victor Chang

Type

Text

Type

Thesis

Advisor

Bowen, Mark E | Miller, W. Todd

Date

2016-12-01

Keywords

NMDAR, Palmitoylation, Phosphonatetheinyl Transferase, PPTase, PSD95 | Biochemistry

Department

Department of Biochemistry and Cell Biology

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/76886

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Signal transduction relies on the proper localization of proteins to properly transfer signals throughout the cell. The cell membrane serves as a vital interface for the proper localization of proteins. Posttranslational modifications cause proteins to become targeted to membranes. One such modification is palmitoylation, the addition of a palmitic acid to a cysteine of a protein. Within the neuron, a large protein complex called the postsynaptic density receives upstream signals at the synapse. Many signaling proteins within the postsynaptic density are known to require palmitoylation for proper trafficking and function. Two such examples are the N-methyl-D-Aspartate receptor (NMDAR) and Post Synaptic Density Protein 95 (PSD95). While studies have been carried out on their soluble forms, their palmitoylated forms have not been well studied. This is due to the difficulty in palmitoylating proteins in-vitro. We circumvent this issue by utilizing phosphopantetheinyl transferases (PPTases) to palmitoyate proteins. PPTases are able to attach various Coenzyme A substrates to proteins with specific tag sequences. We also develop a 2-step assay to quantify the effectiveness of the palmitoylation reaction. We successfully show that palmitoylation using AcpS, a PPTase, is possible utilizing the developed assays. | 47 pages

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