Fundamentals of Molecular Biology. Part 1: Molecular Cell Biology - A. N. Ogurtsov 2011

Transport of substances within the cell
Protein synthesis in the rough endoplasmic reticulum

The presence of Ribosomes on the membranes of the rough Endoplasmic reticulum clearly indicates that this is a site of Protein Synthesis. However, in most cases, the ribosomes of the rough endoplasmic reticulum synthesize Proteins that do not participate in any processes within that given Cell—proteins that are "useless" to it and sometimes even harmful.

For instance, the ribosomes of the rough endoplasmic reticulum in mammary gland Cells synthesize large amounts of milk casein, which is entirely unnecessary for the mammary cells themselves. Similarly, the ribosomes of the rough endoplasmic reticulum in digestive gland cells synthesize hydrolytic Enzymes; if these enzymes were to enter the Cytosol, it would inevitably lead to self-Digestion and cell death.

However, this does not happen because the synthesized proteins are transported across the membrane of the rough endoplasmic reticulum into its lumen, thereby being immediately isolated from the cytosol and cytoplasmic structures.

Thus, the function of the rough endoplasmic reticulum is not merely to synthesize proteins on its membrane-bound ribosomes, but also to segregate these proteins from the rest of The Cell's functional proteins.

A GENERALIZED SCHEME OF METABOLISM/35.html">Protein Biosynthesis is shown in Figure 33.

Protein biosynthesis (mRNA Translation) always begins in the Cytoplasm (Figure 33(1)). A specific sequence of 15–60 Amino Acids at the beginning of the chain, known as the signal peptide, directs the site of synthesis.

If the protein forming on the ribosome begins with a signal peptide (Figure 33(2)) that targets it to the rough endoplasmic reticulum, an RNA-containing signal-recognition particle (SRP) binds to it, and translation is temporarily halted (Figure 33(3)).

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Figure 33 - Protein synthesis in the rough endoplasmic reticulum

The SRP binds the ribosome to the membrane of the rough endoplasmic reticulum via the SRP receptor (Figure 33(4)). As soon as the ribosome anchors to the membrane, the SRP dissociates from both the signal peptide and the SRP receptor (accompanied by GTP Hydrolysis), and translation resumes on the ribosome (Figure 33(5)).

As the polypeptide chain grows on the ribosome and before it has folded, it passes through the membrane via a channel called the translocon into the lumen of the rough endoplasmic reticulum (Figure 33(6)).

Upon completion of translation, the signal peptide of the secretory protein is cleaved off by a specialized enzyme, leader peptidase, preventing the protein from leaving the lumen of the rough endoplasmic reticulum. This process is known as vectorial discharge.

The passage of the growing polypeptide through the membrane can be interrupted by a specific stop-transfer signal. In this case, the polypeptide remains embedded in the membrane, giving rise to an integral membrane protein. During protein synthesis, the growing chain may traverse the membrane multiple times, with synthesis reinitiation mediated by additional signal Peptides. Membrane Proteins formed via this mechanism will possess multiple transmembrane domains.

Most proteins synthesized on the membranes of the rough endoplasmic reticulum are Glycoproteins, whereas soluble cytosolic proteins are not glycosylated. Glycosylation is another major biosynthetic function of The endoplasmic reticulum, and it plays a critical role in determining the subsequent fate of these proteins.