Altered palmitoylation and neuropathological deficits in mice lacking HIP14.

Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are reminiscent of Huntington disease (HD). Palmitoylation of other HIP14 substrates, but not Htt, was reduced in the Hip14-/- mice. Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD.

[1]  Claire-Anne Gutekunst,et al.  Huntingtin-Interacting Protein HIP14 Is a Palmitoyl Transferase Involved in Palmitoylation and Trafficking of Multiple Neuronal Proteins , 2004, Neuron.

[2]  N. Seidah,et al.  Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. , 2001, The Journal of biological chemistry.

[3]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[4]  Louise Wickham,et al.  Post-translational Processing of β-Secretase (β-Amyloid-converting Enzyme) and Its Ectodomain Shedding , 2001, The Journal of Biological Chemistry.

[5]  Maria Karayiorgou,et al.  Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia , 2004, Nature Genetics.

[6]  K. Marder,et al.  Weight loss in early stage of Huntington’s disease , 2002, Neurology.

[7]  Joseph B. Martin,et al.  Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid , 1986, Nature.

[8]  E. Simpson,et al.  Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. , 2003, Human molecular genetics.

[9]  Jane S. Paulsen,et al.  Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[10]  R. Nicoll,et al.  PSD-95 involvement in maturation of excitatory synapses. , 2000, Science.

[11]  M. Hayden,et al.  Cognitive Dysfunction Precedes Neuropathology and Motor Abnormalities in the YAC128 Mouse Model of Huntington's Disease , 2005, The Journal of Neuroscience.

[12]  D. Bredt,et al.  Protein palmitoylation: a regulator of neuronal development and function , 2002, Nature Reviews Neuroscience.

[13]  D. Bredt,et al.  Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95 , 2009, The Journal of cell biology.

[14]  Vincent A Magnotta,et al.  Longitudinal change in regional brain volumes in prodromal Huntington disease , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  W. N. Green,et al.  Labeling and quantifying sites of protein palmitoylation. , 2004, BioTechniques.

[16]  Hillel Adesnik,et al.  Identification of PSD-95 Palmitoylating Enzymes , 2004, Neuron.

[17]  M. Zhuo,et al.  Synaptic Imbalance, Stereotypies, and Impaired Social Interactions in Mice with Altered Neuroligin 2 Expression , 2008, The Journal of Neuroscience.

[18]  G. Quamme,et al.  Huntingtin-interacting Proteins, HIP14 and HIP14L, Mediate Dual Functions, Palmitoyl Acyltransferase and Mg2+ Transport* , 2008, Journal of Biological Chemistry.

[19]  Peter Gustavsson,et al.  Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation , 2005, European Journal of Human Genetics.

[20]  Mark Mühlau,et al.  Striatal gray matter loss in Huntington's disease is leftward biased , 2007, Movement disorders : official journal of the Movement Disorder Society.

[21]  J. Gorski,et al.  Early Striatal Dendrite Deficits followed by Neuron Loss with Advanced Age in the Absence of Anterograde Cortical Brain-Derived Neurotrophic Factor , 2004, The Journal of Neuroscience.

[22]  References , 1971 .

[23]  H. Ropers.  X-linked mental retardation: many genes for a complex disorder. , 2006, Current opinion in genetics & development.

[24]  J. Vonsattel,et al.  Morphometric Demonstration of Atrophic Changes in the Cerebral Cortex, White Matter, and Neostriatum in Huntington's Disease , 1988, Journal of neuropathology and experimental neurology.

[25]  Jiandie D. Lin,et al.  Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators , 2006, Cell.

[26]  B. Austen,et al.  Post‐translational processing of beta‐secretase in Alzheimer's disease , 2005, Proteomics.

[27]  S. Bakar.  Correlating Changes in QNE Scores to Quantified Changes in Hippocampal Surface Area and Volume in Huntington's Disease Patients , 2004 .

[28]  P. Munroe,et al.  Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits. , 1998, Human molecular genetics.

[29]  Peter Redgrave,et al.  Basal Ganglia , 2020, Encyclopedia of Autism Spectrum Disorders.

[30]  R. Mark Henkelman,et al.  Natural history of disease in the YAC128 mouse reveals a discrete signature of pathology in Huntington disease , 2011, Neurobiology of Disease.

[31]  S. Hersch,et al.  HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. , 2002, Human molecular genetics.

[32]  Louise Wickham,et al.  Post-translational processing of β-secretase (BACE) and its ectodomain shedding: the pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid Aβ production , 2001 .

[33]  Shaun S. Sanders,et al.  Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  Lu Gan,et al.  Palmitoylation of huntingtin by HIP14is essential for its trafficking and function , 2006, Nature Neuroscience.

[35]  R. Mark Henkelman,et al.  Automated deformation analysis in the YAC128 Huntington disease mouse model , 2008, NeuroImage.

[36]  M. Linder,et al.  G-protein Palmitoyltransferase Activity Is Enriched in Plasma Membranes (*) , 1996, The Journal of Biological Chemistry.

[37]  J. Penney,et al.  Differential loss of striatal projection systems in Huntington’s disease: a quantitative immunohistochemical study , 2004, Journal of Chemical Neuroanatomy.

[38]  Jane S. Paulsen,et al.  Striatal and white matter predictors of estimated diagnosis for Huntington disease , 2010, Brain Research Bulletin.

[39]  Wilhelm Gaus,et al.  Evidence for more widespread cerebral pathology in early HD: An MRI-based morphometric analysis , 2004, Neurology.

[40]  Linyi Chen,et al.  The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase , 2002, The Journal of cell biology.

[41]  B. Harper.  Huntington Disease , 2005, Journal of the Royal Society of Medicine.

[42]  Yonglan Zheng,et al.  Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8. , 2004, Human molecular genetics.

[43]  Andrew Menzies,et al.  Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. , 2007, American journal of human genetics.