Membrane transport across endoplasmic reticulum

The nucleus of the cell (Figure 1.2) is composed of a porous nuclear membrane, the nucleolus, and soluble materials. The nucleolus contains ribonucleic acids (RNA) and genetic materials also termed chromatin that code for the proteins synthesized upon the ribosomes in the cell cytoplasm. The nuclear membrane is continuous with the outer membrane of the endoplasmic reticulum. Messenger RNA synthesized in the nucleus is transported across the nuclear membrane and is involved in protein synthesis. It fits into the groove between the large and small rRNA subunits (Figure 1.2)... 

In order to provide a better understanding of the role of Ca + as an almost universal regulator of cellular function, we need to take a brief look at the many ways by which Ca ions can be transported in or out of eukaryotic cells. Although various transport pathways have been elucidated, the present picture is probably not complete, since the molecular structures and properties of the transport proteins are only partially known. The major pathways for transport across cellular membranes involve three membrane systems the plasma membrane, the inner mitochondrial membrane, and the membrane of the endoplasmic reticulum (ER) (or, in striated muscle cells, a specialized form of ER called the sarcoplasmic reticulum (SR) (Figure 3.9). Two of the membrane-bound transport systems are Ca " -ATPases, since they derive their main energy from the hydrolysis of ATP (1 and 2 in Figure 3.9). Their properties do, however, differ in many other respects, as we will see. 

Schematic representation of the major pathways for the transport of Ca across cellular membranes. PM, plasma membrane ER(SR), endoplasmic reticulum (sarcoplasmic reticulum) M, mitochondria A P, difference in membrane potential. The transport proteins shown are 1 and 2, PM and ER(SR) Ca -ATPases 3 and 4, PM and ER(SR) receptor-mediated Ca " channels 5 and 6, PM and M (inner-membrane) Na /Ca exchangers 7 and 8, PM and M voltage-sensitive Ca channels. In addition, some not-well-defined passive transport pathways are indicated by dashed arrows.

Fehr, M., Takanaga, H., Ehrhardt, D. W. and Frommer, W. B. (2005b). Evidence for high-capacity bidirectional glucose transport across the endoplasmic reticulum membrane by genetically encoded fluorescence resonance energy transfer nanosensors. Mol. Cell. Biol. 25, 11102-12. 

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 nucleus is surrounded by the nuclear envelope, which takes on a lumenal structure connected to the endoplasmic reticulum. The transport of proteins into (and out of) the nucleus occurs through the nuclear pore complex (NPC), a large complex composed of more than 100 different proteins (Talcott and Moore, 1999). Because NPC forms an aqueous pore across the two membranes, small proteins less than 9 nm in diameter can pass through it simply by diffusion. However, most of the transports of both proteins and RNAs are mediated by an active transport mechanism. It is now clear that there is heavy traffic through the NPC in both directions. Proteins are not only imported into the nucleus but also actively exported from it as well. There are many reasons for nuclear export. One reason is to send some shuttle proteins back after their import another is for some viral proteins to export their replicated genomes outside the nucleus. 

The site of synthesis of numerous proteins is remote from their site of function. During transfer from one site to the other, proteins must, therefore, cross cellular membranes [43] [44], Proteins are usually synthesized as precursors containing an amino terminal extension, called the signal (leader) peptide, the sequence of which contains the necessary information to guide the protein to and across a specific membrane. After transmembrane transport (called translocation), the signal peptide is cleaved off by specific signal peptidases, which are found in the rough endoplasmic reticulum, and the... 

Qu D. Teckman )H, Omura S, Perlmutter DH (1996) Degradation of a mutant secretory protein, a 1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem 271 22791-22795 Rapoport TA, Jungnickel B, Kutay U (1996) Protein transport across the eukaryotic endoplasmic reticulum and bacterial inner membranes. Annu Rev Bioi em 65 271-303... 

In contrast, the hydrocarbon contact sex pheromone of the German cockroach is synthesized in Class II oenocytes associated with the abdominal stemites (Young et al., 1999 Fan et al., 2002). These large oenocytes, ranging up to 50 p in in diameter in B. germanica, have abundant mitochondria and extensive smooth endoplasmic reticulum (Fan et al., 2002). Although the oenocytes are associated with abdominal stemites, the hydrocarbons are released into the hemolymph and loaded, probably across a plasma membrane reticular system, into high-density lipophorin. The lipophorin then likely transports the hydrocarbon to epidermal cells for release onto the cuticle (Fan et al., 2002). 

The large concentration gradient between extracellular spaces and cytosol is maintained by the active transport of Ca2+ across the plasma membrane, the endoplasmic reticulum (or the sarcoplasmic reticulum in muscle), and the mitochondrial inner membrane. Generally, plasma membrane and endoplasmic reticulum each contain a Ca2+-ATPase that actively pumps Ca2+ out of the cytosol at the expense of ATP hydrolysis (7, pp. 496-498). Mitochondria act as a buffer for cytosolic Ca2+ ... 

Figure 22-3. Transport and hepatic metabolism of bilirubin. Bilirubin that is produced in phagocytes is transported to liver as an albumin-bilirubin complex. Uptake into the hepatocytes takes place in liver sinusoids. Within the hepatocyte, bilirubin is transported to the endoplasmic reticulum (microsomes) bound to glutathione S-transferase (GST). Bilirubin is made water soluble by addition of one or two glucuronic acid moieties obtained from UPD-glucuronic acid, catalyzed by bilirubin-UDP-glucuronyltransferase. The product, conjugated bilirubin, is transported across the bile canalicular membrane for secretion into the biliary system, with subsequent movement into the intestines.

Rapoport, T. A. (1992). Transport of proteins across the endoplasmic reticulum membrane. Science 258,931-6. 

Bossuyt X, Blanckaert N. Carrier-mediated transport of uridine diphosphoglucuronic acid across the endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase activity in rat liver. Biochem. J. 1997 323 645-648. 

Like diphtheria toxin. Pseudomonas aeruginosa exotoxin A requires low pH to act (FitzGerald ef al., 1980). In spite of this, it has not been possible to induce translocation of Pseudomonas toxin across the surface membrane by exposure to low pH. It appears that the toxin must be transported beyond the endosomes, possibly to the trans-Golgi network or even to the endoplasmic reticulum to find conditions required for translocation (Chaudhary et al., 1990). In fact domain III ends with an amino acid sequence that (after removal of a terminal... 

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