Secretory proteins, synthesis

Figure 16-6 summarizes our current understanding of secretory protein synthesis and the role of the SRP and its... 

Blockade of morphine dependence-related enhancement of secretory protein synthesis in the pons-medulla and striatum-septum by naltrexone... 

Albumin (69 kDa) is the major protein of human plasma (3.4-4.7 g/dL) and makes up approximately 60% of the total plasma protein. About 40% of albumin is present in the plasma, and the other 60% is present in the extracellular space. The liver produces about 12 g of albumin per day, representing about 25% of total hepatic protein synthesis and half its secreted protein. Albumin is initially synthesized as a preproprotein. Its signal peptide is removed as it passes into the cisternae of the rough endoplasmic reticulum, and a hexapeptide at the resulting amino terminal is subsequently cleaved off farther along the secretory pathway. The synthesis of albumin is depressed in a variety of diseases, particularly those of the liver. The plasma of patients with liver disease often shows a decrease in the ratio of albumin to globulins (decreased albumin-globuhn ratio). The synthesis of albumin decreases rela-... 

Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport. However, not all membrane-bounded organelles (MBOs) are destined for the axon. As a result, the first stage of transport must be synthesis, sorting and packaging of organelles (see Ch. 9). Once assembled, the organelle must then be committed to the transport... 

Transport of MBOs to their various destinations is typically mediated by MTs and motor molecules. Membrane and secretory proteins become associated with membranes either during or immediately following their synthesis, and then maintain this association throughout their lifetime in the cell. For example, inhibiting synthesis of either protein or phospholipid leads to a proportional decrease in the amount of both protein and phospholipid... 

Rusinol, A.E., Cui, Z, Chen, M.H., and Vance, J.E., 1994, A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J. Biol. Chem., 269 27494-27502. 

Figure 10-8 Current version of protein synthesis and processing via ER, Golgi, and secretory vesicles. CGN, ds-Golgi network C, T, M are the cis, medial, and trans compartments of the Golgi stack TGN, trans Golgi network. Arrows indicate some of the movements of transport vesicles.

Secretory proteins have an N-terminal signal peptide which targets the protein to be synthesized on the rough endoplasmic reticulum (RER). During synthesis it is translocated through the RER membrane into the lumen. Vesicles then bud off from the RER and carry the protein to the Golgi complex, where it becomes glycosylated. Other vesicles then carry it to the plasma membrane. Fusion of these transport vesicles with the plasma membrane then releases the protein to the cell exterior. 

Fig. 1. Synthesis and exocytosis of secretory proteins see text for details. The ribosomes attached to the RER are shown as filled-in circles whereas the open circles in the lumen of the ER, vesicles and Golgi complex represent secretory protein molecules.

The mRNA for the secretory protein binds to a free cytoplasmic ribosome and protein synthesis begins. The first part of the protein made is the N-terminal signal peptide. A signal recognition particle (SRP), which is a complex of a 7S RNA and six proteins, binds to the signal peptide and stops further protein synthesis. This stops the secretory protein from being released prematurely into the cytosol. The ribosome-mRNA-SRP complex now binds to an SRP receptor, a protein on the surface of the ER. The ER membrane also contains a ribosome receptor protein associated with a protein translocator. In a concerted series of reactions, the ribosome is held tightly by the ribosome receptor protein, the SRP... 

The enzyme is constitutively expressed in most cell types, but its expression can be induced by an increase in the synthesis of secretory proteins. 

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