Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT

Francisco J. Diaz-Corrales, Ikuko Miyazaki, Masato Asanuma, Diego Ruano, Rosa M. Rios

Research output: Contribution to journalArticle

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Abstract

Lewy bodies containing the centrosomal protein γ-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 γ-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 γ-tubulin aggregates which altered microtubule nucleation. MG132-treated cells containing γ-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.

Original languageEnglish
Pages (from-to)2462-2477
Number of pages16
JournalNeurobiology of Aging
Volume33
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Golgi Apparatus
Tubulin
Microtubules
Parkinson Disease
trans-Golgi Network
Lewy Bodies
Proteasome Inhibitors
Substantia Nigra
Proteasome Endopeptidase Complex
Cell Membrane
Neurons
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Proteins
Therapeutics

Keywords

  • γ-Tubulin
  • Aggresome
  • Centrosome
  • Dopamine transporter
  • Golgi apparatus
  • Inclusion bodies
  • Lewy bodies
  • Microtubules
  • Neurodegeneration
  • Parkinson's disease
  • Proteasome
  • Protein aggregation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT. / Diaz-Corrales, Francisco J.; Miyazaki, Ikuko; Asanuma, Masato; Ruano, Diego; Rios, Rosa M.

In: Neurobiology of Aging, Vol. 33, No. 10, 10.2012, p. 2462-2477.

Research output: Contribution to journalArticle

Diaz-Corrales, Francisco J. ; Miyazaki, Ikuko ; Asanuma, Masato ; Ruano, Diego ; Rios, Rosa M. / Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 10. pp. 2462-2477.
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