Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington's disease.

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).

• Authors: Junmei Wan, Jeffrey N Savas, Amy F Roth, Shaun S Sanders, Roshni R Singaraja, Michael R Hayden, John R Yates 3rd, Nicholas G Davis
• Journal: Chemistry & biology (Chem Biol) Vol. 20 Issue 11 Pg. 1421-34 (Nov 21 2013) ISSN: 1879-1301 [Electronic] United States
• PMID: 24211138 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Palmitic Acid
• Acyltransferases
• HIP14 protein, mouse

Topics

• Acyltransferases (genetics, metabolism)
• Animals
• Brain (metabolism, pathology)
• Disease Models, Animal
• Huntington Disease (genetics, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuroglia (metabolism)
• Palmitic Acid (metabolism)