Abnormal α-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease

被引:80
作者
Dalfó, E
Barrachina, M
Rosa, JL
Ambrosio, S
Ferrer, I
机构
[1] Hosp Univ Bellvitge, Inst Neuropatol, Serv Anat Patol, Barcelona 08907, Spain
[2] Unitat Neuropatol Expt, Dept Biol Cellular & Anat Patol, Barcelona, Spain
[3] Univ Barcelona, Unitat Bioquim, Dept Ciencies Fisiol 2, Barcelona, Spain
关键词
alpha-synuclein; rab3a; rab5; rab8; rabphilin; Lewy body disease;
D O I
10.1016/j.nbd.2004.01.001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study examines alpha-synuclein interactions with rab3a and rabphilin by antibody arrays, immunoprecipitation and pull-down methods in the entorhinal cortex of control cases and in diffuse Lewy body disease (LBD) cases. alpha-Synuclein immunoprecipitation revealed alpha-synuclein binding to rabphilin in control but not in LB cases. Immunoprecipitation with rab3a disclosed rab3a binding to rabphilin in control but not in LB cases. Moreover, rab3a interacted with high molecular weight (66 kDa) alpha-synuclein only in LB cases, in agreement with parallel studies using antibody arrays. Results were compared with pull-down assays using His(6)/Flag-tagged rab3, rab5 and rab8, and anti-Flag immunoblotting. Weak bands of 17 kDa, corresponding to alpha-synuclein, were obtained in LB and, less intensely, in control cases. In addition, alpha-synuclein-immunoreactive bands of high molecular weight (36 kDa) were seen only in LB cases after pull-down assays with rab3a, rab5 or rab8. These findings corroborate previous observations showing rab3a-rabphilin interactions in control brains, and add substantial information regarding decreased binding of rab3a to raliphilin and increased binding of rab3a to alpha-synuclein aggregates in LB cases. Since, alpha-synuclein, rab3a and raliphilin participate in the docking and fusion of synaptic vesicles, it can be suggested that exocytosis of neurotransmitters may be impaired in LB diseases. Published by Elsevier Inc.
引用
收藏
页码:92 / 97
页数:6
相关论文
共 65 条
  • [1] Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system
    Abeliovich, A
    Schmitz, Y
    Fariñas, I
    Choi-Lundberg, D
    Ho, WH
    Castillo, PE
    Shinsky, N
    Verdugo, JMG
    Armanini, M
    Ryan, A
    Hynes, M
    Phillips, H
    Sulzer, D
    Rosenthal, A
    [J]. NEURON, 2000, 25 (01) : 239 - 252
  • [2] Tubulin seeds α-synuclein fibril formation
    Alim, MA
    Hossain, MS
    Arima, K
    Takeda, K
    Izumiyama, Y
    Nakamura, M
    Kaji, H
    Shinoda, T
    Hisanaga, S
    Uéda, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (03) : 2112 - 2117
  • [3] Baba M, 1998, AM J PATHOL, V152, P879
  • [4] THE MOLECULAR MACHINERY FOR SECRETION IS CONSERVED FROM YEAST TO NEURONS
    BENNETT, MK
    SCHELLER, RH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) : 2559 - 2563
  • [5] Cabin DE, 2002, J NEUROSCI, V22, P8797
  • [6] Accumulation of insoluble α-synuclein in dementia with Lewy bodies
    Campbell, BCV
    Li, QX
    Culvenor, JG
    Jäkälä, P
    Cappai, R
    Beyreuther, K
    Masters, CL
    McLean, CA
    [J]. NEUROBIOLOGY OF DISEASE, 2000, 7 (03) : 192 - 200
  • [7] EVIDENCE THAT THE RAB3A-BINDING PROTEIN, RABPHILIN3A, ENHANCES REGULATED SECRETION - STUDIES IN ADRENAL CHROMAFFIN CELLS
    CHUNG, SH
    TAKAI, Y
    HOLZ, RW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (28) : 16714 - 16718
  • [8] Clayton DF, 1999, J NEUROSCI RES, V58, P120, DOI 10.1002/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO
  • [9] 2-E
  • [10] The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease
    Clayton, DF
    George, JM
    [J]. TRENDS IN NEUROSCIENCES, 1998, 21 (06) : 249 - 254