Golgi Apparatus and Disease

what is the golgi apparatus?

processing and sorting hub

transport and targeting of the soluble cargo proteins and lipids

central role in secretory pathway

alterations to structure and functions affect homeostasis of cellular proteins and lipids

what is the structure of the golgi apparatus?

Characterisation – cisternal membrane structures forming Golgi stack, surrounded by vesicles
• Distribution- based on resident proteins
Divided into 3 regions- cis, medial and trans-Golgi cisternae
Vertebrate cells – Golgi stacks are laterally interconnected by tubular membranes –Golgi ribbon
• Golgi ribbon structure is supported by Golgi matrix
• Golgi matrix – dynamic structural proteins- integrity and vesicular trafficking

what are the two main functions of the golgi apparatus?

1. Posttranslational protein modification –glycan processing throughout Golgi stacks
2. Sorting, Packing, Routing, and recycling-modified cargo to appropriate cellular destinations

what are vesicular transport models of the golgi?

golgi cisternae are static; cargo are transported through them by COPI vesicles

what are cisternal maturation models of the golgi?

cisternae are dynamic structures, while golgi enzymes are recycle via retrograde transport of COPI vesicles

what is golgi fragmentation in ALS?

presence in patient motor neurones

association with specific ALS-linked mutations

vulnerability of larger human motor neurones

implications for disease pathogenesis

what are the impairments of cellular trafficking for golgi fragmentation in ALS?

Sensitivity of ER-Golgi Compartments
Implications on Cellular Homeostasis
Evidence Linking Impairment to Golgi Fragmentation
Specific Mechanisms in ALS Mutant Proteins
Disruption of Protein Sorting and Processing
Overall Impact on Cellular Function
Therapeutic Implications

what is golgi fragmentation and autophagy dysfunction in ALS?

Role of the Golgi in Autophagosome Biogenesis
• Potential Implications of Golgi Fragmentation on Autophagy Dysfunction
• Relationship Between Golgi Fragmentation and Autophagy Regulation
• Highlighting Contradictory Observations
• Potential Pathological Links in ALS
• Therapeutic Implications

what is axonal homeostasis?

Specialized Role of the Golgi in Maintaining Axonal Homeostasis
• Impact on Synaptic Plasticity
• Potential Impact of Golgi Fragmentation on Axonal Functions
• Relevance to ALS-Related Axonal Degeneration
• Implications for Axonal Transport
• Potential Impact on Synaptic Dysfunction
• Therapeutic Implications

what are the specific ALS- linked mutations associated with golgi fragmentation?

SOD1 (Chr 21), TDP-43 (Chr 1), FUS (Chr 16), and C9orf72 (Chr 9)