title: Memory and synaptic deficits in Hip14/DHHC17 knockout mice.
abstract: Palmitoylation of neurotransmitter receptors and associated scaffold proteins regulates their membrane association in a rapid, reversible, and activity-dependent fashion. This makes palmitoylation an attractive candidate as a key regulator of the fast, reversible, and activity-dependent insertion of synaptic proteins required during the induction and expression of long-term plasticity. Here we describe that the constitutive loss of huntingtin interacting protein 14 (Hip14, also known as DHHC17), a single member of the broad palmitoyl acyltransferase (PAT) family, produces marked alterations in synaptic function in varied brain regions and significantly impairs hippocampal memory and synaptic plasticity. The data presented suggest that, even though the substrate pool is overlapping for the 23 known PAT family members, the function of a single PAT has marked effects upon physiology and cognition. Moreover, an improved understanding of the role of PATs in synaptic modification and maintenance highlights a potential strategy for intervention against early cognitive impairments in neurodegenerative disease.
authors.affiliation: Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Austen J
authors.initials: AJ
authors.lastname: Milnerwood
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Parsons
authors.forename: Fiona B
authors.initials: FB
authors.lastname: Young
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: Sonia
authors.initials: S
authors.lastname: Franciosi
authors.forename: Mattia
authors.initials: M
authors.lastname: Volta
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bergeron
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Raymond
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D003712:Dendrites / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D054878:Lipoylation; D017774:Long-Term Potentiation / Q000235:genetics* / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000235:genetics* / Q000502:physiology
chemical_list: D000217:Acyltransferases; C569387:Zdhhc17 protein, mouse
keywords: Huntington disease; hippocampus; long-term potentiation; posttranslational modification; striatum