Fragmentation of the Golgi ribbon is a common feature of many neurodegenerative diseases but little is known about the causes of this alteration. In Parkinson's disease, it is believed to be the consequence of an ER-Golgi transport imbalance and/or of cytoskeleton alterations. In the present study, we analyze the mechanisms involved in Golgi fragmentation in differentiated PC12 cells treated with 6-hydroxydopamine or methamphetamine as cellular models of Parkinson's disease. Our data demonstrate that Golgi fragmentation precedes and might trigger the aggregation of α-synuclein and the formation of inclusions, alterations in anterograde and retrograde transport between the endoplasmic reticulum and Golgi complex, and cytoskeleton damage. In contrast, fragmentation is directly related with alterations in the levels of Rab1, 2 and 8 and the SNARE protein syntaxin 5. Thus, overexpression of Rab1 and 8 and depletion of Rab2 and syntaxin 5 rescue the Golgi morphology. In conclusion, the homeostasis of a limited number of Rab and SNARE proteins is important for understanding the cytopathology of Parkinson's disease.

In most mammalian cells, the Golgi complex forms a continuous ribbon. In neurodegenerative diseases, the Golgi ribbon of a specific group of neurons is typically broken into isolated elements, a very early event which happens before clinical and other pathological symptoms become evident. It is not known whether this phenomenon is caused by mechanisms associated with cell death or if, conversely, it triggers apoptosis. When the phenomenon was studied in diseases such as Parkinson’s and Alzheimer’s or amyotrophic lateral sclerosis, it was attributed to a variety of causes, including the presence of cytoplasmatic protein aggregates, malfunctioning of intracellular traffic and/or alterations in the cytoskeleton. In the present review, we summarize the current findings related to these and other neurodegenerative diseases and try to search for clues on putative common causes.

Lipids and lipid-modifying enzymes play a key role in the biogenesis, maintenance and fission of transport carriers in the secretory and endocytic pathways. In the present study we demonstrate that phosphatidic acid generated by phospholipase D2 (PLD2) is involved in the formation of Golgi tubules. The main evidence to support this is: 1) inhibitors of phosphatidic acid formation and PLD2 depletion inhibit the formation of tubules containing resident enzymes and regulators of intra-Golgi transport in a low temperature (15°C) model of Golgi tubulation but do not affect brefeldin A-induced tubules, 2) inhibition of PLD2 enzymatic activity and PLD2 depletion in cells cultured under physiological conditions (37°C) induce the formation of tubules specifically containing Golgi matrix proteins, and, 3) over-expression of PLD2 induces the formation of a tubular network. In addition, it was found that the generation of this lipid by the isoenzyme is necessary for ArfGAP1 recruitment to Golgi membranes. These results suggest that both proteins are involved in the molecular mechanisms which drive the formation of different types of Golgi tubules.

Principal epididymal cells have one of the largest and more developed Golgi complex of mammalian cells. In the present study, we have used this cell as model for the study of the three-dimensional architecture of the Golgi complex of highly secretory and endocytic cells. Electron tomography demonstrated the presence in this cell type of some unknown or very unusual Golgi structures such as branched cisternae, pocket-like cisternal invaginations or tubular connections. In addition, we have used this methodology and immunoelectron microscopy to analyze the close relationship between this organelle and both the endoplasmic reticulum and microtubules, and to describe in detail how these elements interact with compact and non-compact regions of the ribbon.