The ER membrane separates the inside (lumen) from the cytosol. The ER is composed of Rough ER (RER) and Smooth ER. RER has ribosomes attached to the outside surface; it is these ribosomes that synthesise the secretory proteins (SP). The SP are either destined for the cytoplasm, cell membrane or externally, to be targeted to other parts of the body, usually via the bloodstream. Proteins are also synthesised by "free ribosomes" which exist in the cytosol and are not part of the RER. The SP are separated from the free ribosome proteins by the ER membrane. The SP are in their raw stage. Modification occurs in the Golgi apparatus (GA)
Proteins synthesised in the ER reach the GA in transport vesicles. The vesicles separate from the ER by being "pinched off" from the ER membrane. It moves to the GA, to which it fuses and deposits the protein into. The GA modifies, stores, indexes and distributes the protein. The index provides a "post-code", ensuring it arrives at the correct location. The GA has a CIS face, which faces the ER and is the receiving side for the SP, the opposite side of the GA is the Trans face, (the distribution side). The proteins are modified during their movement from the CIS to Trans face.
MEMBRANE
The GA also produces lysosomes. After modification in the GA the proteins are ready for transport, in protected vesicles, either as lysosomes or targeted at the membrane for use as an integral protein or external secretion by exocytosis. Exocytosis causes the secretory proteins to fuse with the cell membrane and release its contents, usually into the blood stream, for delivery to the correct destination.
Protein targeting (PT) or protein sorting is undertaken either in the ER-GA processing route (biosynthetic secretory pathway). This is co-translational targeting (CTT). Secretory proteins must be sent to the correct destination within an organism for them to function correctly. In CTT, the protein synthesised has a signal sequence attached. A signal recognition particle (SRP) is released form the cytosol. The SRP attaches to the ribosome, translation temporarily stops. The SRP docks with a docking-protein on the ER, the signal sequence penetrates the ER membrane, the SRP is released by the enzyme protease and synthesis continues.
Post-translational targeting (PTT) is when cytosolic proteins, synthesised by free ribosomes, remain in the cytosol and are bound for membrane bound organelles, eg, the mitochondria. When the protein reaches its intended destination, it must cross the organelle's membrane without folding. Another protein, a chaperone, attaches to the newly synthesised protein to prevent it from folding. An SRP attaches to the protein as in CTT and is released by protease. The chaperone detaches from the protein once it has penetrated the organelle membrane and the protein folds to the correct shape.
So far, one way trafficking has been described, ie, exocytosis. Endocytosis plays a part in delivering products to the inside of the cell from outside the cell membrane by invagination of the cell membrane to form vesicles. This can be achieved by Pinocytosis, phagocytosis or receptor mediated Endocytosis (RME).
Pinocytosis brings extra cellular fluids into the cell. The vesicles are protected by smaller protein molecules called clathrin, released once inside the cell, subsequently releasing the fluids. The cell utilises the molecules dissolved in the fluid.
Phagocytosis produces larger vesicles than Pinocytosis and is responsible for engulfing dead cells, cell debris and pathogens for destruction and recycling by enzymes within the cell.
RME provides bulk quantities of products, eg. low density lipoproteins (LDL). On the external cell membrane there are slight depressions called coated pits. Receptor proteins are also present on the pits. Using LDL molecules as an example, the pits form a vesicle which surrounds the LDL. The vesicle is strengthened by clathrin particles, released when the LDL macromolecule enters the cell. After ingestion of the LDL, the receptors reach the plasma membrane in the same vesicles for recycling.
Conclusion
From the integration of amino acids in the nucleus to the completion of proteins in the ER. The synthesis is fine-tuned in the GA for transport to either the cell membrane as integral proteins or the exterior of the cell to be targeted at specific areas within the eukaryotic organism. Free ribosomes within the cytosol synthesise proteins for use by the cell's internal organelles. The newly synthesised proteins in both cases arrive at the right location due to indexing by the GA and cytosol respectively.
Protein Targeting and Membrane Trafficking MEMBRANE
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