Ribosome endoplasmic reticulum—bound

Potter, M. D., and Nicchitta, C. V. (2002). Endoplasmic reticulum-bound ribosomes reside in stable association with the translocon following termination of protein synthesis. J. Biol. Chem. 277, 23314-23320. 

The rest of the known sequences of all four classes of BCB domain-containing proteins feature signal peptides in their precursors, indicating that they are translocated across the bacterial cytoplasmic membrane or are translated on the endoplasmic reticulum-bound ribosomes and sent to the secretory pathway in eukaryotes. Thus they are located in the bacterial periplasm, secreted into the extracellular milieu, or anchored to the cell surface. 

Three organelles may be considered within this section the ribosome, endoplasmic reticulum and Golgi apparatus (Figure 9.2). The ribosomes may be found free in the cytoplasm or attached to membranes especially the endoplasmic reticulum (ER). Free ribosomes participate in the synthesis of intracellular proteins whilst ribosomes bound to the ER synthesize proteins destined for the cell surface as membrane components or secretions and lysosomes. The structure (Section 7.4) and function of ribosomes (Section 17.6) in either case is the same. 

Surprisingly, it turned out that some of peroxisomal membrane proteins are synthesized at the ER, cotranslationally. This seems a unique example that breaks the independence between the free ribosome system and the membrane-bound ribosome system (another example is found in a sorting mechanism into the vacuole). This phenomenon may be interpreted that the peroxisome may originate from the endoplasmic reticulum, evolutionally. 

Protein processing in the endoplasmic reticulum makes mistakes. All membrane-associated proteins and proteins that are secreted by the cell are synthesised on membrane-bound ribosomes and pass into the lumen of the reticulum, where they are modified by post-translational processes, so that much biochemical manipulation of the proteins takes place. Consequentially mistakes are often made. Such abnormal proteins are exported from the lumen into the cytosol for ubiquitination and degradation in the proteasome. 

The endoplasmic reticulum (ER) is an extensive closed membrane system consisting of tubular and saccular structures. In the area of the nucleus, the ER turns into the external nuclear membrane. Morphologically, a distinction is made between the rough ER (rER) and the smooth ER (sER). Large numbers of ribosomes are found on the membranes of the rER, which are lacking on the sER. On the other hand, the sER is rich in membrane-bound enzymes, which catalyze partial reactions in the lipid metabolism as well as biotransformations. 

Regions of the ER that have no bound ribosomes are known as the smooth endoplasmic reticulum (sER). In most cells, the proportion represented by the sER is small. A marked sER is seen in cells that have an active lipid metabolism, such as hepatocytes and Leydig cells. The sER is usually made up of branching, closed tubules. 

Secretory and membrane-tai eted proteins are synthesized as larger precursors on endoplasmic reticulum (ER)—bound ribosomes, which inject the protein across or into the ER membrane as it is translated. 

Protein synthesis can be carried out by ribosomes free in the cytosol. In eukaryotes, ribosomes also carry out protein synthesis while bound to the surface of the endoplasmic reticulum. In addition, a given mRNA molecule usually has more than one active ribosome translating it into protein an assembly of several ribosomes on a single mRNA is called a polyribosome, or polysome for short. 

The synthesis of the apoproteins takes place on ribosomes that are bound to the endoplasmic reticulum. As we mentioned previously, the biosynthesis of the other lipids in lipoproteins (cholesterol, triacylglycerols, and phospholipids) also occurs on the endoplasmic reticulum. 

Since collagen is a secreted protein, we know that it must follow the route of synthesis that starts on a ribosome bound to the endoplasmic reticulum (fig. 29.23). This is where the fun begins, as we find that the nascent collagen polypeptide has extensive N and C termini (150 and 250... 

Translating ribosomes in eukaryotes are located in different places in the cell depending on the fate of their proteins. Free polysomes are in the cytoplasm and synthesize cytoplasmic proteins and those that are bound for most intracellular organelles, for example, the nucleus. Members of the second class of polysomes, membrane-bound polysomes, are attached to the endoplasmic reticulum (forming the rough ER), and synthesize exported proteins. In cells that are actively secreting enzymes or hormones (for example, those in the pancreas), most of the protein synthesis occurs on the rough ER. 

The reactions of phase 2 relate to the attachment of the bridge-carbohydrate residues to the polypeptide chain. There is evidence showing that this addition occurs while the polypeptide chain is still attached to, or perhaps still being synthesized on, the ribosomes.101-103 Thus, 14C-labeled 2-amino-2-deoxy-D-glucose, injected into the circulatory system of the rat, was incorporated into protein in the ribosomes of the rough endoplasmic-reticulum of the liver. Administration of puromycin caused release of the 14C-labeled glycoprotein, which could be isolated by acid-precipitation methods. Examination of the radioactivity data revealed that the subcellular structures most actively involved in glycoprotein synthesis were the ribosomes bound to the membrane, and not free polysomes. 

The amino acids of a protein control its location in the cell. Some proteins are water soluble, whereas others are bound to the ceil membrane (plasma membrane), the mitochondrial membrane, and the membranes of the endoplasmic reticulum and nucleus. The association of a protein with a membrane is maintained by a stretch of lipophilic amino acids. Insertion of this stretch into the membrane occurs as the protein is synthesized. Water-soluble proteins are formed on ribosomes that "float" free in the cytoplasm. Membrane-bound proteins are formed on ribosomes that associate with the endoplasmic reticulum (ER). As the amino acids are polymerized in the vicinity of the F,R, a stretch of lipophilic acids becomes inserted into the membrane of the FR. This anchoring of the protein is maintained when it is shuttled from its location in the ER to its desired location in the plasma membrane. 

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