Poster Presentations

Session Title: Neurodevelopment and Neurodegeneration
Presentation Date: Friday, March 14 – Saturday, March 15, 2009

EFFECT OF PROTEASOME INHIBITION IN GOLGI APPARATUS AND CENTROSOME STRUCTURE - RELEVANCE IN PARKINSON´S DISEASE PATHOPHYSIOLOGY

F. Diaz-Corrales¹, M.P. Gavilan¹, D. Ruano², R.M. Rios^1
1Centro Andaluz de Biología Molecular y Medicina Regenerativa, Señalizacion Celular, Sevilla, Spain, ²Facultad de Farmacia- Universidad de Sevilla, Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Sevilla, Spain

Parkinson´s disease (PD) is characterized by progressive loss of dopaminergic neurons. Cytological hallmarks of this disease are the presence of protein aggregates known as Lewy bodies, that contain γ-tubulin, and fragmentation of the Golgi Apparatus (GA). It is well-known that the centrosome and the GA maintain a intimate relationship in mammalian cells. However, the mechanisms responsible of GA/centrosome perturbations in PD are unknown. We have analysed GA fragmentation and γ-tubulin aggregation in the neuroblast SH-SY5Y cells treated with the proteasome inhibitor MG132. Several constitutive proteins of GA, centrosome and MT cytoskeleton were tested by immunofluorescence and Western blotting. In non-treated cells, an intact Golgi ribbon located near to the centrosome was observed (Figure 1I). On the contrary, MG132 treatment induced GA fragmentation and γ-tubulin aggregation in a dose-dependent manner (1J-L). Interestingly, GA fragmentation was observed under conditions in which γ-tubulin aggregates were not present (Fig 1C-D), suggesting that this is not a consequence of MT-network perturbation. Confocal analysis also revealed an early and dramatic effect on the trans side of the GA. In addition, membrane traffic pathways connecting the ER with the cell surface appeared perturbed in treated cells. These results might be relevant for understanding GA dysfunction in PD.

[EFFECT OF PROTEASOME INHIBITION IN GOLGI APPARATUS]