期刊
NEUROBIOLOGY OF AGING
卷 33, 期 10, 页码 2462-2477出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.11.014
关键词
Aggresome; Centrosome; Dopamine transporter; gamma-Tubulin; Golgi apparatus; Inclusion bodies; Lewy bodies; Microtubules; Neurodegeneration; Parkinson's disease; Proteasome; Protein aggregation
资金
- Consejo Superior de Investigaciones Cientificas (CSIC), Spain
- Consejeria de Innovacion Ciencia y Empresa, Proyecto de Excelencia, Spain [P07-CVI-03199]
- Ministerio de Ciencia e Innovacion, Spain [BFU2009-07182]
- Consolider, Spain [CSD2009-00016]
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [24111533, 22590934, 24659431, 21591082] Funding Source: KAKEN
Lewy bodies containing the centrosomal protein gamma-tubulin and fragmentation of Golgi apparatus (GA) have been described in nigral neurons of Parkinson's disease (PD) patients. However, the relevance of these features in PD pathophysiology remains unknown. We analyzed the impact of proteasome inhibition in the formation of gamma-tubulin-containing aggregates as well as on GA structure. SH-SY5Y cells were treated with the proteasome inhibitor Z-Leu-Leu-Leu-al (MG132) to induce centrosomal-protein aggregates. Then, microtubules (MTs) and Golgi dynamics, as well as the vesicular transport of dopamine transporter (DAT) were evaluated both in vitro and in living cells. MG132 treatment induced gamma-tubulin aggregates which altered microtubule nucleation. MG132-treated cells containing gamma-tubulin aggregates showed fragmentation of GA and perturbation of the trans-Golgi network. Under these conditions, the DAT accumulated at the centrosomal-Golgi region indicating that the vesicular transport of DAT was disrupted. Thus, centrosomal aggregates and fragmentation of GA are 2 closely related processes that could result in the disruption of the vesicular transport of DAT toward the plasma membrane in a model of dopaminergic neuronal degeneration. (C) 2012 Elsevier Inc. All rights reserved.
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