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NIDA Proteomics Center
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Investigators
> William N. Green
Proteomic Assays of Neuronal
Protein Palmitoylation
William N. Green, Department of Neurobiology,
University of Chicago
Protein palmitoylation is a reversible,
post-translational process in which the fatty acid, palmitate, is linked
covalently to proteins. As a result, palmitoylation regulates membrane
association of proteins and their partitioning into membrane domains such as
lipid rafts. There is mounting evidence that palmitoylation has a major role in
neuronal development and function, in particular, the formation, regulation and
functioning of synapses. Because synapses in brain reward regions are thought to
undergo changes that underlie drug abuse we would like to examine whether
palmitoylation of synaptic proteins and/or their regulatory proteins changes
during drug abuse. The animal model of drug abuse to be used is the phenomenon
of sensitization induced in rats by exposure to amphetamine. We have recently
developed new techniques for assaying protein palmitoylation that are
quantitative and more sensitive than other approaches. Furthermore, these
techniques can be used to assay the palmitoylation of proteins from brain for
the first time.
The main objective of these proposed experiments
is to develop proteomic assays based on our new techniques that will address
questions about the palmitoylation of ionotropic neurotransmitter receptors and
the palmitoylation of proteins found in large-scale protein preparations from
brain such as postsynaptic densities (PSDs) and lipid rafts. New proteomic-based
technology will be developed to assay a protein post-translational modification.
Ultimately we hope to use these techniques to characterize the role of
palmitoylation in the molecular mechanisms underlying drug abuse. Specifically,
we plan to use these techniques to assay for the synaptic proteins isolated from
rat nucleus accumbens that undergo changes in their palmitoylation with
amphetamine exposure.
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