Abstract
Protein palmitoylation, a reversible lipid modification of proteins, is widely used in the nervous system, with dysregulated palmitoylation being implicated in a variety of neurological disorders. Described below is ABE/SILAM, a proteomic strategy that couples acyl-biotinyl exchange (ABE) purification of palmitoyl-proteins to whole animal stable isotope labeling (SILAM) to provide an accurate tracking of palmitoylation change within rodent disease models. As a first application, we have used ABE/SILAM to look at Huntington's disease (HD), profiling palmitoylation change in two HD-relevant mouse mutants: the transgenic HD model mouse YAC128 and the hypomorphic Hip14-gt mouse, which has sharply reduced expression for HIP14 (Zdhhc17), a palmitoyl-transferase implicated in the HD disease process. Rather than mapping to the degenerating neurons themselves, the biggest disease changes instead map to astrocytes and oligodendrocytes (i.e., the supporting glial cells).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1421-1434 |
| Number of pages | 14 |
| Journal | Chemistry and Biology |
| Volume | 20 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 21 2013 |
Funding
We thank Robin (Sung Kyu) Park for his expert help with the Census program. Grant support for this work was provided by the NIH (R01GM65525 to N.G.D., R01MH067880 to J.R.Y., P41-GM103533 to J.R.Y., and F32-AG039127 to J.N.S.) and Canadian Institutes of Health Research (CIHR) grant GPG-102165. Fellowship support was provided by both the CIHR and the Michael Smith Foundation for Health Research (to S.S.S.). M.R.H. is a Killam University Professor and holds a Canada Research Chair in Human Genetics and Molecular Medicine.
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Molecular Biology
- Biochemistry
- Clinical Biochemistry
- Pharmacology