Endoplasmic reticulum binding

EXAMPLE 6.5 Inositol trisphosphate (IP3) is often produced by cells in response to the binding of an extracellular ligand to a cell membrane receptor (see Sec. 6.3). Receptors for IP3 are located on the membranes of the endoplasmic reticulum. Binding of IP3 to these receptors leads to the release of Ca + from stores in the lumen of the endoplasmic reticulum. The IP3 receptor is therefore an example of a ligand-gated ion channel (see below)... 

Chaperones. Figure 2 The multiple roles of BiP in the biogenesis of the secretory proteins. BiP, immunoglobulin heavy chain binding protein ER, endoplasmic reticulum ERAD, ER-associated degradation ERj, resident ER protein with J-domain Sec61, core subunit of the protein translocase UPR, unfolded protein response that involves several signal transduction pathways that are activated in order to increase the biosynthetic capacity and decrease the biosynthetic burden of the ER... 

Ryanodine receptor (RyR) is an intracellular Ca2+ release channel in the sarcoplasmic reticulum (SR) or the endoplasmic reticulum (ER). RyR binds ryanodine (a plant alkaloid, see Drugs) with a high affinity, after which it is named. 

The signal recognition particle (SRP) is a cytosolic ribonucleoprotein complex which binds to signal sequences of nascent membrane and secretory proteins emerging from ribosomes. The SRP consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72 kD). It induces an elongation arrest until the nascent chain/ ribosome/SRP complex reaches the translocon at the endoplasmic reticulum (ER) membrane. 

Figure 3. Reporting of intracellular calcium sequestration by chlorotetracycline (CTC). CTC preferentially partitions into cell membranes and its fluorescence in this environment is sensitive to calcium bound to the membrane therefore its signal (excitation AOO nm, emission 530 nm) will come largely from organelles that bind or sequester calcium, such as smooth endoplasmic reticulum or mitochondria. Release of calcium from such organelles is accompanied by dissociation of the calcium-CTC complex, a decrease in CTC fluorescence and efflux of unbound probe from the organelle and from the cell.

Brodifacoum, difenacoum, flocoumafen, and other superwarfarins bind strongly to proteins of the hepatic endoplasmic reticulum and consequently have long half-lives in vertebrates, often exceeding 100 days. Thus, they present a hazard to predators and scavengers that feed on rodents which have been exposed to superwarfarins. A number of species of predatory and scavenging birds have died as a consequence... 

THE SIGNAL HYPOTHESIS EXPLAINS HOW POLYRIBOSOMES BIND TO THE ENDOPLASMIC RETICULUM... 

In the family of cation pumps, only the Na,K-ATPase and H,K-ATPase possess a p subunit glycoprotein (Table II), while the Ca-ATPase and H-ATPase only consist of an a subunit with close to 1 000 amino acid residues. It is tempting to propose that the p subunit should be involved in binding and transport of potassium, but the functional domains related to catalysis in Na,K-ATPase seem to be contributed exclusively by the a subunit. The functional role of the P subunit is related to biosynthesis, intracellular transport and cell-cell contacts. The P subunit is required for assembly of the aj8 unit in the endoplasmic reticulum [20]. Association with a j8 subunit is required for maturation of the a subunit and for intracellular transport of the xP unit to the plasma membrane. In the jSl-subunit isoform, three disulphide... 

The GABAb receptor is not a single 7TM receptor but rather a heterodimer formed by two 7TM receptors from family C. The GABAb-R1 receptor, which was initially cloned, binds the ligand GABA, but when expressed alone it is to a large extent retained in the endoplasmic reticulum,... 

Hayashi, T., Su, T.-P. Sigma-1 receptors (sigma-1 binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum roles in endoplasmic reticulum lipid compartmen-talization and export. J. Pharmacol. Exp. Ther. 306 718, 2003. 

Wearsch PA, Voglino L, Nicchitta CV (1998) Structural transitions accompanying the activation of peptide binding to the endoplasmic reticulum Hsp90 chaperone GRP94. Biochemistry 37(16) 5709-5719... 

Stephens, S. B., Dodd, R. D., Brewer, J. W., Lager, P. J., Keene, J. D., and Nicchitta, C. V. (2005). Stable ribosome binding to the endoplasmic reticulum enables compartment-specific regulation of mRNA translation. Mol. Biol. Cell 16, 5819—5831. 

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