DJ-1 associates with membrane trafficking system.

2012 Fiscal Year Final Research Report

• Project/Area Number: 23700389
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience in general
• Research Institution: Juntendo University
• Principal Investigator: HATANO Taku 順天堂大学, 医学部, 准教授 (60338390)
• Project Period (FY): 2011 – 2012
• Keywords: DJ-1 / 家族性パーキンソン病 / 膜輸送 / シナプトソーム / synaptophysin / Rab3A

Research Abstract

Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons. Although many reports have suggested that genetic factors are implicated in the pathogenesis of PD, molecular mechanisms underlying selective dopaminergic neuronal degeneration remain unknown. DJ-1 is a causative gene for autosomal recessive form of PARK7-linked early-onset PD. In this project, my colleagues and I revealed that DJ-1 distributes to the cytosol and membranous structures in a punctate appearance in cultured cells and in primary neurons obtained from mouse brain. Additionally, DJ-1 colocalizes with GM130, synaptophysin and Rab3A. Forster resonance energy transfer analysis revealed that a small portion of DJ-1 interacts with synaptophysin in living cells. Although the wild-type DJ-1 protein directly associates with membranes without an intermediary protein, the pathogenic L166P mutation of DJ-1 exhibits less binding to synaptic vesicles. These results indicate that DJ-1 associates with membranous organelles including synaptic membranes to exhibit its normal function.

Research Products

• [Journal Article] PINK1 autophosphorylation facilitates Parkin recruitment ot mitochondria: new insight in the mechanisms of quality control for mitochondria in young-onset Parkinosn's disease (2012)
  • Author(s): Hatano T.
  • Journal Title: Mov Disord Volume: 27 Pages: 1613
• [Journal Article] Levodopa-responsive Parkinsonism following bilateral putaminal hemorrhages (2012)
  • Author(s): Hatano T, Kubo SI, Niijima-Ishii Y, Hattori N, Sugita Y
  • Journal Title: Parkinosnism Relat Disord Volume: (in press)
• [Journal Article] Distinct mechanisms of axonal globule formation in mice expressing human wild tupe -synuclein or dementia with lewy bodies-linked P123H-synclein. (2012)
  • Author(s): Sekigawa A, Fujita M, Sekiyama K, Takamatsu Y, Hatano T, Rochenstein E, La Spada AR, Mashiah E, Hashimoto M
  • Journal Title: Mol Brain Volume: 5 Pages: 34
  • DOI: DOI:10.1186/1756-6606-5-34.
• [Journal Article] VPS35 mutation in Japanese patients with typical Parkinos's disease (2012)
  • Author(s): Ando M, Funayama M, Li Y, Kashihara K, Murakami Y, Ishizu N, Toyoda C, Noguchi K, Hashimoto T, Nakano N, Sasaki R, Kokubo Y, Kuzuhara S, Ogaki K, Yamashita C, Yoshino H, Hatano T, Tomiyama H, Hattori N.
  • Journal Title: Mov Disord Volume: 27 Pages: 1413-7
• [Journal Article] Urinary homocysteic Acid levels correlate with mini-mental state examination scores in Alzheimer's disease patients (2012)
  • Author(s): Hasegawa T, Ichiba M, Matsumoto SE, Kasanuki K, Hatano T, Fujishiro H, Iseki E, Hattori N, Yamada T, Tabira T.
  • Journal Title: J Alzheimers Dis Volume: 31(1) Pages: 59-64
• [Journal Article] Young Japanese Expert Group for Parkison's Disease and Movement Disorders: YJ-EXPANDS. Validity and reliability assessment of a Japanese version of the Snaith-Hamilton pleasure scale (2012)
  • Author(s): Nagayama H, Kubo S, Hatano T, Hamada S, Maeda T, Hasegawa T, Kadowaki T, Terashi H, Yoshioka M, Nomoto N, Kano O, Inoue M, Shimura H, Takahashi T, Uchiyama T, Watanabe H, Kaneko S, Takahashi T, Baba Y
  • Journal Title: Intern Med Volume: 51 Pages: 865-9
• [Journal Article] LRRK2 I2020T mutation is associated with tau pathology (2012)
  • Author(s): Ujiie S, Hatano T, Kubo SI, Imai S, Sato S, Uchihara T, Yagishita S, Hasegawa K, Kowa H, Sakai F, Hattori N.
  • Journal Title: Parkinsonism Relat Disord Volume: 18 Pages: 819-23
• [Journal Article] Pramipexole reduces the prevalence of fatigue in patients with Parkinson's disease (2011)
  • Author(s): Morita A, Okuma Y, Kamei S, Yoshii F, Yamamoto T, Hashimoto S, Utusmi H, Hatano T, Hattori N, Matsumura M, Takahashi K, Nogawa S, Watanabe Y, Miyamoto M, Hirata K.
  • Journal Title: Intern Med Volume: 50 Pages: 2163-8
• [Journal Article] The effect of Ndrg2 expression on astroglial activation (2011)
  • Author(s): Takeichi T, Takarada-Iemata M, Hashida K, Sudo H, Okuda T, Kokame K, Hatano T, Takanashi M, Funabe S, Hattori N, Kitamura O, Kitao Y, Hori O
  • Journal Title: Neurochem International Volume: 59 Pages: 21-7
• [Journal Article] Atypical Miller Fisher syndrome assocaited with glutamate receptor antibodies (2011)
  • Author(s): Hatano T, Shimada Y, Kono A, Kubo S, Yokoyama K, Yoritaka A, Nakahara T, Takahashi Y, Hattori N
  • Journal Title: BMJ Case Rep 2011
  • DOI: DOI:pii: bcr0820103228. 10.1136/bcr.08.2010.3228.
• [Journal Article] A novel protein degradation system in young-onset Parkinosn's disease: mitophagy is a therapeutic target as a quality control for damaged mitochondria (2011)
  • Author(s): Hatano T
  • Journal Title: Mov Disord Volume: 26 Pages: 773
• [Journal Article] DJ-1 associates with synaptic membranes (2011)
  • Author(s): Usami Y, Hatano T, Imai S, Kubo S, Sato S, Saiki S, Fujioka Y, Ohba Y, Sato F, Funayama M, Eguchi H, Shiba K, Ariga H, Shen J, Hattori N
  • Journal Title: Neurobiol of Dis Volume: 43 Pages: 651-62
• [Book] Etiology and pathogenesis of Parkinson's disease. In: Rana AQ, ed.Etiology and pathophysiology of Parkinson's disease. (2011)
  • Author(s): Hatano T and Hattori N
  • Total Pages: 1-14
  • Publisher: Rijeka: INTECH
• [Book] Parkinson Disease (2011)
  • Author(s): Hatano T and Hattori N
  • Publisher: In eLS. Chichester: Johon Wiley & Sons