title: Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins.
abstract: In neurons, posttranslational modification by palmitate regulates the trafficking and function of signaling molecules, neurotransmitter receptors, and associated synaptic scaffolding proteins. However, the enzymatic machinery involved in protein palmitoylation has remained elusive. Here, using biochemical assays, we show that huntingtin (htt) interacting protein, HIP14, is a neuronal palmitoyl transferase (PAT). HIP14 shows remarkable substrate specificity for neuronal proteins, including SNAP-25, PSD-95, GAD65, synaptotagmin I, and htt. Conversely, HIP14 is catalytically invariant toward paralemmin and synaptotagmin VII. Exogenous HIP14 enhances palmitoylation-dependent vesicular trafficking of several acylated proteins in both heterologous cells and neurons. Moreover, interference with endogenous expression of HIP14 reduces clustering of PSD-95 and GAD65 in neurons. These findings define HIP14 as a mammalian palmitoyl transferase involved in the palmitoylation and trafficking of multiple neuronal proteins.
authors.affiliation: Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Anat
authors.initials: A
authors.lastname: Yanai
authors.forename: Rujun
authors.initials: R
authors.lastname: Kang
authors.forename: Pamela
authors.initials: P
authors.lastname: Arstikaitis
authors.forename: Roshni R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: Martina
authors.initials: M
authors.lastname: Metzler
authors.forename: Asher
authors.initials: A
authors.lastname: Mullard
authors.forename: Brendan
authors.initials: B
authors.lastname: Haigh
authors.forename: Catherine
authors.initials: C
authors.lastname: Gauthier-Campbell
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Gutekunst
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Husseini
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D019308:Palmitic Acid; D000217:Acyltransferases; C473038:ZDHHC17 protein, human; D002334:Carnitine O-Palmitoyltransferase