Abstract
The Golgi apparatus is an essential cellular organelle for post-translational modifications, sorting, and trafficking of membrane and secretory proteins. Proper functionality of the Golgi requires the formation of its unique cisternal-stacking morphology. The Golgi structure is disrupted in a variety of neurodegenerative diseases, suggesting a common mechanism and contribution of Golgi defects in neurodegenerative disorders. A recent study on Alzheimer's disease (AD) revealed that phosphorylation of the Golgi stacking protein GRASP65 disrupts its function in Golgi structure formation, resulting in Golgi fragmentation. Inhibiting GRASP65 phosphorylation restores the Golgi morphology from Aβ-induced fragmentation and reduces Aβ production. Perturbing Golgi structure and function in neurons may directly impact trafficking, processing, and sorting of a variety of proteins essential for synaptic and dendritic integrity. Therefore, Golgi defects may ultimately promote the development of AD. In the current review, we focus on the cellular impact of impaired Golgi morphology and its potential relationship to AD disease development.
Highlights
The Golgi apparatus is a membranous cellular organelle that mediates proper trafficking, posttranslational processing, and sorting of membrane and secretory proteins
We summarize the current literature on the cause and effect of Golgi fragmentation in Alzheimer’s disease (AD), the leading cause of dementia in adults (Alzheimer’s, 2015)
One neuropathological hallmark of AD is the formation of extracellular amyloid plaques by secreted amyloid beta (Aβ) peptides (Nelson et al, 2009), which is highly related to Golgi structure and function (Figure 1)
Summary
The Golgi apparatus is a membranous cellular organelle that mediates proper trafficking, posttranslational processing, and sorting of membrane and secretory proteins. Golgi membranes form multilayer stacks that are laterally linked into a ribbon. Formation of stable multilayer stacks and ribbons appears to be essential for proper functioning of the Golgi (Rambourg et al, 1987; Ladinsky et al, 1999; Klumperman, 2011; Klute et al, 2011). Disruption of normal Golgi morphology directly impacts protein trafficking and processing. Golgi defects may impact the trafficking and processing of many proteins essential for neuronal functions. Understanding the mechanisms that cause Golgi fragmentation and its downstream effects on neuronal functions are likely important for understanding the molecular basis of the diseases. We summarize the current literature on the cause and effect of Golgi fragmentation in AD, the leading cause of dementia in adults (Alzheimer’s, 2015)
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