| Abstract No.: | A-B1031 |
| Country: | Canada |
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| Title: | NEURONAL PALMITOYL-PROTEOMICS: DYNAMIC MODULATION OF PALMITOYLATION AT THE SYNAPSE |
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| Authors/Affiliations: | 2 Rujun Kang*; 4 Junmei Wan; 2 Pamela Arstikaitis; 2 Hideto Takahashi; 2 Kun Huang; 3 William N. Green; 1 John R. Yates; 4 Nicholas G. Davis; 2 Alaa El-Husseini;
1 The Scripps Research Institute, USA; 2 University of British Columbia, Vancouver, BC, Canada; 3 University of Chicago, IL, USA; 4 Wayne State University School of Medicine, USA
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| Content: | Palmitoylation, a reversible protein modification by the lipid palmitate, regulates diverse aspects of neuronal protein trafficking and function1-4. A full understanding of the impact of this modification on neuronal function has been precluded by difficulties in predicting and detecting palmitoylation. Here, we apply acyl-biotin exchange (ABE) proteomic technology to purify and identify palmitoyl-proteins (PPs) for global characterization of the neuronal palmitoyl-proteome5. This analysis identifies most of the known neuronal PPs, 68 in total, and over 200 new PP candidates, with palmitoylation being confirmed for 20 of these through additional testing. New PPs include neurotransmitter receptors, transporters, adhesion molecules, scaffolding, vesicle proteins, and SNARE proteins that mediate vesicular trafficking. Of particular interest is the identification of a brain enriched splice variant of cdc42 that regulates spine maturation by reversible palmitoylation. Palmitoylated cdc42 is more potent than the canonical prenyl isoform in spine induction, shows higher GTPase activity, and is discretely localized to dendritic spines. Palmitoylation of cdc42 is regulated by neuronal activity, which controls the amount of cdc42 localized at the synapse. Finally, we uncover differences in palmitoyl-regulation in response to various drug-induced changes in neuronal activity both in cultured neurons and in vivo. Our findings identify palmitoylation as a key modifiable signal on many synapse-enriched proteins that contribute to activity-driven changes in synapse morphology and function. |
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