The golgi apparatus is a membrane bound organelle found in most cells. It has a function in packaging proteins and is implicated in the secretory pathway.
In this article we shall look at the structure and function of the golgi apparatus and its role in Wilson’s disease.
The golgi is made of 5-8 folds called cisternae. The cisternae contain specific enzymes creating five functional regions which modify proteins passing through them in a stereotypical way, as follows:
- Cis-Golgi network: faces the nucleus, forms a connection with the endoplasmic reticulum and is the entry point into the Golgi apparatus.
- Cis-Golgi: major processing area allowing biochemical modifications
- Medial-Golgi: major processing area allowing biochemical modifications
- Trans-Golgi: major processing area allowing biochemical modifications
- Trans-Golgi network: exit point for vesicles budding off the Golgi surface, packages and sorts biochemicals into the vesicles according to their destination
The golgi apparatus modifies proteins and lipids from the endoplasmic reticulum. These biochemicals leave the golgi by exocytosis before being delivered to different intracellular (such as to lysosomes) or extracellular (such as to the cell membrane) locations.
- Protein processing – carbohydrate regions of glycoproteins are altered by addition, removal or modification of carbohydrates such as the phosphorylation of mannose in lysosomal proteins and O-linked glycosylation to aid vesicle trafficking
- Lipid processing – adds phosphate groups and glycoproteins to lipids from the endoplasmic reticulum (such as cholesterol) to create the phospholipids that make up the cell membrane
Sorting, Budding and Exocytosis
Biochemicals are chemically labelled in the golgi to ensure appropriate delivery to the correct destination. Once they bud off the trans Golgi they will enter a specific pathway according to this label.
Lysosomal proteins – such as enzymes are packaged into specific vesicles. These proteins are typically tagged with mannose-6-phosphate in the Golgi
Secretory proteins – such as hormones are packaged into secretory vesicles ready for exocytosis. This requires ATP as two negatively charged membranes need to fuse to allow their release. The membrane of the vesicle will form part of the cell membrane. This is only possible in Golgi of secretory cells
Cell surface proteins – such as phospholipids enter the constitutive secretory pathway present in all cells
Clinical Relevance – Wilson’s Disease
Wilson’s disease is an autosomal recessive disorder characterised by an abnormal accumulation of copper in the body. The liver is particularly susceptible to this accumulation.
Mutation of the ATP7B gene is implicated in the development of Wilson disease. The ATP7B gene codes for copper-transporting ATPase 2 (also known as Wilson disease protein or WDP), an enzyme located in the Golgi apparatus of many cells such as hepatocytes and neurones.
Wilson disease protein normally allows copper to bind to caeruloplasmin, a protein which transports copper to various parts of the body. If copper levels are too high, WDP leaves the Golgi, allowing copper to be excreted in bile instead of transported around the body.
Patients experience symptoms and signs of liver failure, such as itching, abdominal swelling, fatigue, jaundice, ascites and Kayser-Fleischer rings (deposition of copper in the cornea).
They may also present with neuropsychiatric symptoms such as confusion, psychosis, personality changes and tremor. Copper may also accumulate in joints causing joint pain and swelling.
Diagnosis is based on abnormal liver function tests, serum copper levels, urinary copper levels, and serum caeruloplasmin levels. If the diagnosis is unclear a liver biopsy may be indicated.
Management is aimed at reducing copper levels using copper chelating agents such as penicillamine.