title: 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.affiliation: Department of Pharmacology, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Junmei
authors.initials: J
authors.lastname: Wan
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Savas
authors.forename: Amy F
authors.initials: AF
authors.lastname: Roth
authors.forename: Shaun S
authors.initials: SS
authors.lastname: Sanders
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Davis
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*
chemical_list: D019308:Palmitic Acid; D000217:Acyltransferases; C569387:Zdhhc17 protein, mouse