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

Junmei Wan, Jeffrey N. Savas, Amy F. Roth, Shaun S. Sanders, Roshni R. Singaraja, Michael R. Hayden, John R. Yates, Nicholas G. Davis*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

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 languageEnglish (US)
Pages (from-to)1421-1434
Number of pages14
JournalChemistry and Biology
Volume20
Issue number11
DOIs
StatePublished - Nov 21 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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