Overview Of The Golgi Apparatus
The Golgi apparatus, found in all eukaryotes, is a key organelle consisting of a parallel series of flattened cisternal membranes with vesicles and tubes on the periphery. Its structure of disk-shaped cisternae and enzymes on them mirrors the function, as enzymes on the cis face begin the process of sorting secretory substances for transport ,intermediate steps are carried out by enzymes in the medial portion, and the final steps are performed on the trans cisternae side with enzymes there. Two major structural models for the Golgi apparatus are the stable compartments model, which views the Golgi apparatus as several distinct sets of sub-organelles which secretory substances travel hrough, and the cisternal maturation model which accounts for problems with the previous model, such as large secretory substances which would need transport on mega vesicles that there is no evidence of.
Atomic Force Microscopy(AFM) has confirmed the many vesicles surrounding the outer edges of Golgi apparatus for transport, as well as revealed the dense proteins on the inside and smooth surface on the outer leaflet. Lipid rafts contain regions of related proteins, and Detergent Resistant Membranes (DRM) were found using time-lapse AFM. Major functions of the Golgi apparatus include sorting and processing newly synthesized membrane and secretory particles. The protein orientations found, especially the asymmetry which reveals the polarized Golgi vesicles, contribute to the Golgi apparatus’s membrane sorting and signaling functions, essential for the exchange of substances and membrane fusion (24). The Golgi apparatus and endoplasmic reticulum work closely together in eukaryotic cells, as endoplasmic reticulum sites begin the transport of secretory particles.
The Golgi apparatus is dependent on cycling of components through the endoplasmic reticulum, or else the proteins would need to redistribute through the ER. In addition, the Golgi apparatus further modifies the N-linked oligosaccharides of glycoproteins added to the proteins within the endoplasmic reticulum. When vesicles from the endoplasmic reticulum fuse, vesicular tubular clusters form and deliver proteins, then may return to the endoplasmic reticulum using ER retrieval signals which may directly interact with different vesicles or other proteins. Lipid metabolism, including the synthesis of glycolipids and sphingomyelin by from ceramide, is another major function of the Golgi apparatus. The lumenal surface is responsible for synthesis of sphingomyelin, a non-glycerol phospholipid essential for signaling pathways, and the cytosolic surface is responsible forthe synthesis of ceramide. Both are localized to the exterior of the plasma membrane, with polar heads at the cell’s surface, after vesicular transport because they are unable to translocate themselves. The sorting of proteins is a necessary step of protein transport from the Golgi apparatus as well, another function of the Golgi apparatus. A secretory pathway allows proteins and lipids to travel to the cell surface and become part of the plasma membrane, contributing to the fluid mosaic model of the cell membrane.
Trafficking within the Golgi cisternae is essential for stages of maturation, contributing to cisternal assembly in mammalian cells, carbohydrate synthesis mediated by COPIb vesicles, and carrier formation which is defined by the packaging of cargo onto carriers. Although stacking of Golgi cisternaeis not necessary for a cell to survive, it is essential for protein trafficking and processing. Certain inhibition causing destruction of these cisternae stacks may cause protein missorting because it accelerates the protein trafficking. As a result, defects may be very severe. Because the Golgi apparatus is so important for proteins and carbohydrates, linked diseases with defects of the Golgi apparatus include degenerative diseases such as ALS (amyotrophic lateral sclerosis), Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. This causes fragmentation of Golgi ribbon and atrophy, or loss of the material from the Golgi membrane.
The fragmentation of Golgi apparatus’s cisternae may be associated with structural alterations and impaired functions due to the need for protein trafficking throughout the cell, and it is apparent in Alzheimer’s disease cases. This is related to the misfolding that may occur in the endoplasmic reticulum. The amyloid plaques formed and secreted mark Alzheimer’s disease, and they are derived from amyloid precursor protein which matures by the Golgi apparatus and may bind and localize when the Golgi apparatus is not properly functioning. In addition, neurofibrillary tangles (NFTS) are another distinction of Alzheimer’s related to the Golgi apparatus. Abnormal hyperphosphorylation of tau blocks transport and microtubule integrity, which the Golgi apparatus is reliant on. This results in Golgi fragmentation as well.
In the long term, the fluid mosaic of the cell membrane may be altered negatively, impairing neuron activity and recognition functions, which may lead to cell death because of an immune response (34). The study of Golgi defects inrelation to Alzheimer’s disease may provide more treatments. For example, in one study Cdk5 activation was suppressed, inhibiting the phosphorylation of GRASP65 and thus preventing Golgi fragmentation, which resulted in the reduction of amyloid beta secretion because of amyloid precursor protein cleavage elevation. This study suggests targeting the Golgi apparatus with drugs, and this may apply to other neurodegenerative diseases caused by defects of the Golgi apparatus.
The cell membrane, or plasma membrane, consists of an amphipathic phospholipid bilayer made up of hydrophilic heads, hydrophobic tails, and proteins used for many specific functions embedded on the surface. Cell membrane lipids on the outer side of the cellular membrane also regulate cell membrane function: cholesterolis needed to regulate ion pumps and the fluidity of the phospholipid bilayer, and phosphatidyl-ethanolamine is needed to regulate membrane protein activity. Because of the way the cellular membrane consists of these specialized membrane domains, the fluid mosaic model is the accepted visual model. Different domains may focus on different functions or interactions such as lipid-lipid and protein-lipid interactions.
The structure of the phospholipid bilayer matches its function of semi permeability. The hydrophobic interior makes the membrane impermeable to water-soluble molecules. The double bonds found in phospholipids make them unsaturated fat which contains kinks on the hydrocarbon tails. This causes the membrane to not pack together as tightly and be flexible as opposed to rigid. In animal cells, cholesterol regulates the fluidity of the phospholipid fatty acid chains so that temperature changes do not result in drastic effects. The rigid ring structure of cholesterol allows certain organisms to adapt to different environmental conditions.
Proteins embedded on the surface of the plasma membranes help to carry out a variety of the essential functions, such as transport, cell-cell recognition, attachment to the extracellular matrix, and more (35). The synthesis of cell membranes is dependent on the manufacture inside the endoplasmic reticulum. Similarly, the cell membrane relies on the endoplasmic reticulum, Golgi apparatus, and lysosomes to transport and synthesize substances such as essential proteins.
Membrane proteins and lipids are synthesized by the endoplasmic reticulum and transported by vesicles. The Golgi apparatus modifies and synthesizes membrane proteins and secreted proteins and directs them to their intended domains.
Another important function of the cell membrane is its semi permeability, which protects the cell from its extracellular environment by enclosing organelles into a membrane and maintaining a constant internal environment. Its structure allows it to ensure that necessary nutrients or essential molecules like glucose enter the cell while avoiding toxic substances and releasing waste product. As a result, the structure of the cellular membrane controls the metabolism of the cell, because all its processes and interactions into and out of the cell are controlled by it.
Huntington’s disease, caused by expansion of the cytosine-adenine-guanine trinucleotide, is a neurodegenerative disorder which results in altered lipid metabolism and protein degradation. Many neurodegenerative disorders are caused by impairment of the lipid homeostasis. As with other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, protein misfolding may result in the buildup of them in tissues or other areas, later forming toxic aggregates. Recently, research has shown that Huntington’s disease effects metabolism and disrupts glucose intake as a result, along with lipid metabolism. Although the specific alteration of lipid metabolism in Huntington’s disease is linked to its dysfunction, this remains controversial.
Recently, the fluidity of cell membrane was investigated using fluorescent dyes, and the shift observed correlated with depletion of the cholesterol on the membranes. In other words, Huntington’s disease cells become more fluid, which may be due to the membrane’s hunting tin aggregates, so they may contribute to the fluidity of the membranes in the cells.
Although further testing and retesting is needed, the membrane fluidity was observed to increase and this could be related to defective transport mechanisms of lipids. Although there is currently no cure for Huntington’s disease based on these findings, there is possibility of using these findings to guide future drug discoveries or to contribute to designs of certain drugs by focusing on where the drug must attack.
