Endoplasmic reticulum sorting

A major sorting decision is made early in protein biosynthesis, when specific proteins are synthesized either on free or on membrane-bound polyribosomes. This results in two sorting branches called the cytosolic branch and the rough endoplasmic reticulum (R R) branch (Figure 46-1). This sorting occurs because proteins synthesized on membrane-bound polyribosomes contain a signal peptide that mediates their attachment to the membrane of the ER. Further details on... 

Figure 46-1. Diagrammatic representation of the two branches of protein sorting occurring by synthesis on (1) cytosolic and (2) membrane-bound polyribosomes. The mitochondrial proteins listed are encoded by nuclear genes. Some of the signals used in further sorting of these proteins are listed in Table 46-4. (ER, endoplasmic reticulum GA, Golgi apparatus.)...

Figure 46-6. Flow of membrane proteins from the endoplasmic reticulum (ER) to the cell surface. Horizontal arrows denote steps that have been proposed to be signal independent and thus represent bulkflow. The open vertical arrows in the boxes denote retention of proteins that are resident in the membranes of the organelle indicated. The open vertical arrows outside the boxes indicate signal-mediated transport to lysosomes and secretory storage granules. (Reproduced, with permission, from Pfeffer SR, Rothman JE Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annu Rev Biochem 1987 56 829.)...

Membrane proteins inside transport vesicles bud off the endoplasmic reticulum on their way to the Golgi final sorting of many membrane proteins occurs in the trans-Golgi network. 

This gene is broadly distributed in skeletal muscle, heart, uterus, and in a variety of non-muscle cells. The mRNA levels are particularly high in intestine, lung and spleen, whereas they are very low in liver, testes, kidney and pancreas. In the muscle tissue SERCA3 may be confined primarily to non-muscle cells (vascular smooth muscle, endothelial cells, etc.). The C-terminus of SERCA3 is Asp-Gly-Lys Lys-Asp-Leu-Lys (Table I) it may serve as a sorting signal for retention of the enzyme in the endoplasmic reticulum [57]. 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

The biosynthetic, secretory pathway is responsible for protein sorting and delivery and allows, among other functions, for cell-cell communication through secreted products. This delivery process starts at the endoplasmic reticulum (ER), to finish in the cell plasma membrane or, in some cases, in specific intracellular organelles. To accomplish this, specific proteins must be properly directed to the correct destination, while other proteins are retained as residents within specific organelles along the way. 

Teasdale, R. D. and lackson, M. R. Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus. Ann. Rev Cell Dev. Biol. 12 27-54,1996. 

Saraste, J. and Kuismanen, E. Pathways of protein sorting and membrane traffic between the rough endoplasmic reticulum and the Golgi complex. Semin. Cell Biol. 3 343-355,1992. 

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. 

Dtirr G, Strajde J, Plemper R, Elbs S, Klee SK, Catty P, Wolf DH, Rudolph HK (1998) The medial-Golgi ion pump Pmrl supplies the yeast secretory pathway with Ca2-f- and Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell 9 1149-1162... 

It seems likely that the enzyme complexes for hemicelluloses, pectins and cellulose are constructed, at least in part, on the endoplasmic reticulum and then transferred to the Golgi apparatus, where they are modified and sorted so that they can be segregated within the compartments of the Golgi cisternae (30,31). The complex for cellulose synthesis is not normally active within the Golgi apparatus and it is transported to active sites at the plasma membrane (1). The hemicelluloses and pectins are formed within vesicles and cisternae of the Golgi apparatus and the vesicles are transported to the plasma membrane, where fusion occurs and the polysaccharides are packed into the wall (1). It is not known whether particular polysaccharides such as the xylans of the hemicellulose and the arabinogalactans of the pectins are transported in separate vesicles or together in one vesicle. Nor is it known if the complex for cellulose synthesis is transported by vesicles which carry hemicellulose and pectin polysaccharides. 

Put very simply two sorts of drug-metabolizing enzymatic processes occur in the microsomes of the smooth endoplasmic reticulum or in the cytosol of liver cells. The first, so-called Phase F, reactions may add or subtract a small portion of the drug molecule, commonly by oxidation. This by itself may make a product more water-soluble, but, more commonly, a second step - Phase IF- process is required in which the altered drug is coupled (conjugated - literally married ) to compounds already existing in the liver cells to form salts such as glu-curonides and sulphates (Fig. 3). 

How does the cell sort and transport phospholipids from the site of synthesis to other membranes in the cell One view is that phospholipid vesicles that bud from the endoplasmic reticulum are targeted to another membrane where the vesicles fuse with the membrane. Alternatively, phospholipid transfer proteins may be involved. Proteins that transfer phospholipids between membranes in vitro have been known for over 25 years but it has not been demonstrated that they function in this way in vivo. 

Pelham, H. R. B., Control of protein exit from the endoplasmic reticulum. Ann. Rev. Cell. Biol. 5 1, 1989. Describes the current picture of how proteins are sorted and transported through the endoplasmic reticulum. 

Pfeffer, S. R., and J. E. Rothman, Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Ann. Rev. Biochem. 56 829, 1987. An excellent overview of the major features of protein targeting in eukaryotic cells. 

Poutska F, Irani NG, Feller A, Lu Y, Pourcel L, Frame K, Grotewold E. 2007. A trafficking pathway for anthocyanins overlaps with the endoplasmic reticulum-to-vacuole protein-sorting route in Arabidopsis and contributes to the formation of vacuolar inclusions. Plant Physiol 145 1323-1335. 

Golgi complex Organelles in animal cells composed of a series of fattened sacs that sort, chemically modify, and package proteins produced on the rough endoplasmic reticulum. 

Golgi apparatus is a membrane-enclosed organelle in the endoplasmic reticulum of eukaryotic cells where proteins are modified post-transcriptionally, mainly by glyco-sylation, and where proteins and lipids are sorted for transport to their destinations. 

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