Functional Analysis of a Novel Ubiquitin Specific Protease Related to Alzheimer Disease

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Shinshu University
• Principal Investigator: TIAN Qing Bao Shinshu University, Graduate School of Medicine Department of Neuroplasticity, Assistant Professor, 大学院・医学研究科, 助手 (40324264)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Tatsuo Shinshu University, Graduate School of Medicine Department of Neuroplasticity, Professor, 大学院・医学研究科, 教授 (80162965)
• Project Period (FY): 2003 – 2004
• Keywords: Neurodegeneration / Ubiquitin / Proteasome / Parkinson's Disease / Aggresome / Ubiquitin Specific Protease / Post Synaptic Density

Research Abstract

Recent reports suggest an important role for protein ubiquitination in synaptic plasticity. We cloned, from the rat brain, a novel gene that encoded an ubiquitin-specific protease (USP), and termed this protein synaptic ubiquitin-specific protease (synUSP, GenBank TM Accession no. AB073880). The homologous human gene was mapped to a locus on chromosome 1p36.12. The deduced synUSP protein consisted of 1036 amino acids, and possessed an ubiquitin-like domain at the C-terminus, Cys-and His-boxes, leuane zipper motifs, and six amino add-repeats of L/ILCPHG. The protein possessed de-ubiquitinating activity toward a model substrate, as expected from its sequence. The protein of 125 kDa was present in the rat brain ; in particular, it was enriched in the post-synaptic density and the dendritic lipid raft fractions. The immunostaining of cortical neurons confirmed the postsynaptic localization. The mRNA for synUSP was localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the post-synaptic compartments. These results suggest a regulatory mechanism for the ubiquitin-related system at the post synaptic sites.

Research Products

• [Journal Article] p55 protein is a member of PSD scaffold proteins in the rat brain and interacts with various PSD proteins. (2005)
  • Author(s): Zhang JP, Tian QB, Sakagami H, Kondo H, Endo S, Suzuki T.
  • Journal Title: Molecular Brain Research (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein n complex with various postsynaptic density proteins. (2005)
  • Author(s): Suzuki T, Li W, Zhang JP, Tian QB, Sakagami H, Usada N, Kondo H, Fujii T, Endo S.
  • Journal Title: European Journal Neuroscience 21 Pages: 399-350
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with, but not, subunit of Ca2+/calmodulin-dependent protein kinase II. (2005)
  • Author(s): Wang X, Tian QB, Okano A, Sakagami H, Moon S, Kondo H, Endo S, Suzuki T.
  • Journal Title: Journal of Neurochemistry 92 Pages: 647-659
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with, but not, subunit of Ca2+/calmodulin-dependent protein kinase II. (2005)
  • Author(s): Wang X, Tian B, Okano A, Sakagami H, Moon S, Kondo H, Endo S, Suzuki T.
  • Journal Title: J Neurochem 92 (3) Pages: 647-659
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel scaffold protein, TANG, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins. (2005)
  • Author(s): Suzuki T, Li W, Zhang JP, Tian QB, Sakagami H, Usada N, Kondo H, Fujii T, Endo S.
  • Journal Title: Eur J Neurosci 21 (2) Pages: 339-350
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] p55 protein is a member of PSD scaffold proteins in the rat brain and interacts with various PSD proteins. (2005)
  • Author(s): Zhang JP, Tian QB, Sakagami H, Kondo H, Endo S, Suzuki T.
  • Journal Title: Mol Brain Res (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NIDD, a novel DHHC-containing protein, targets neuronal nitric oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. (2004)
  • Author(s): Saitoh F, Tian QB, Okano A, Sakagami H, Kondo H, Suzuki T.
  • Journal Title: Journal of Biological Chemistry 279 Pages: 29461-29468
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Brain-specific potential guanine nucleotide exchange factor for Arf, synArfGEF(Po), is localized to postsynaptic density. (2004)
  • Author(s): Inaba Y, Tian B, Okano A, Zhang JP, Sakagami H, Miyazawa S, Li W, Komiyama A, Inokuchi K, Kondo H, Suzuki T
  • Journal Title: J Neurochem 89 (6) Pages: 1347-1357
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NIDD, a novel DHHC-containing protein, targets neuronal nitric oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. (2004)
  • Author(s): Saitoh F, Tian QB, Okano A, Sakagami H, Kondo H, Suzuki T.
  • Journal Title: J Biol Chem 279 (28) Pages: 29461-29468
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel ubiquitin-specific protease, synUSP, is localized at the post-synaptic density and post-synaptic lipid raft. (2003)
  • Author(s): Tian QB, Okano A, Nakayama K, Miyazawa S, Endo S, Suzuki T
  • Journal Title: Journal of Neurochemistry 87 Pages: 665-675
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel ubiquitin-specific protease, synUSP, is localized at the post-synaptic density and post-synaptic lipid raft. (2003)
  • Author(s): Tian B, Okano A, Nakayama K, Miyazawa S, Endo S, Suzuki T.
  • Journal Title: J Neurochem 87 (3) Pages: 665-675
  • Description: 「研究成果報告書概要(欧文)」より