Protein translocation endoplasmic reticulum

The UPS also plays a major role in protein quality control. In a process known as endoplasmic associated degradation (ERAD), misfolded proteins, which are formed in the endoplasmatic reticulum, are translocated back to the cytoplasm and degraded by the proteasome. 

Walter, P., and Blobel, G. (1981a). Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J. Cell Biol. 91, 557-561. 

From overexpression studies, it can be inferred that individual isoforms of PKC are precisely directed to distinct subcellular locations (e.g. PKCa to the endoplasmic reticulum and PKCS to the Golgi). Directing PKC isozymes to specific subcellular loci appears to occur via interaction of the enzyme with localized intracellular binding proteins. Such proteins may or may not be substrates for PKC. An example of the latter category would be RACK (receptors for activated C kinase) 1. RACKs are thought to interact only with activated PKCs and to direct translocated PKCs to specific loci. 

Kuroiwa, T., Sakaguchi, M., Mihara, K., and Omura, T. (1991). Systematic analysis of stop-transfer sequence for microsomal membrane. Biol. Chem. 266, 9251—9255. Kuroiwa, T., Sakaguchi, M., Omura, T., and Mihara, K. (1996). Reinitiation of protein translocation across the endoplasmic reticulum membrane topogenesis of multispan-ning membrane proteins. J. Biol. Chem. 271, 6243—6248. 

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... 

Sommer, T. and Jentsch, S. A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 1993, 365, 176-79. 

Answer B. Decreased Factor V secretion and a corresponding accumulation of cytoplasmic antigen suggest a defect in the translocation of the nascent protein to the endoplasmic reticulum. This implies a mutation in the N-terminal amino acid signal sequence required for targeting to the ER and encoded by the first exon of the gene. 

The phosphatidylcholine in bile is synthesised in the endoplasmic reticulum of the hepatocyte and must be transported to the canalicular membrane. One possibility involves the nonspecific phosphatidylcholine transfer protein but a mouse null for this protein did not show reduced phosphatidylcholine secretion into bile and there was no compensatory increase in other phospholipids transfer proteins. However, the plasma membrane would receive a ready supply of phospholipid by insertion of vesicles, and the MDR3 protein translocates this molecule from the inner leafiet to the outer surface where there is contact with bile acids, as suggested by Smit and colleagues. The role of this transporter is shown in Figure 2.2. 

The path that leads from full sized protein to epitopes at the cell surface is complex, consisting of the generation of small peptides, translocation of the peptides to the endoplasmic reticulum by a transporter complex, loading of the peptides onto MHC class-I molecules and relocation of the MHC class-I-peptide complex to the cell surface (Rock and Goldberg, 1999). Since many of these steps are known to be prime targets for viral evasion strategies, the next step was to identify at what point the GAr interferes with the presentation of EBNAl. 

Hagting A, Karlsson C, Clute P, Jackman M, Pines J (1998) MPF localization is controlled by nudear export. EMBO J 17 4127-4138 Hamman BD, Chen JC, Johnson EE, Johnson AE (1997) The aqueous pore through the translocon has a diameter of 40-60 A during cotranslational protein translocation at the ER membrane. Cell 89 535-544 Hampton RY, Rine J (1994) Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J Cell Biol 125 299-312... 

Werner ED, Brodsky JL, McCracken AA (1996) Proteasome-dependent endoplasmic reticulum-associated protein degradation an unconventional route to a familiar fate. Proc Natl Acad Sd USA 93 13797-13801 Wesche J, Rapak A, Olsnes S (1999) Dependence of ridn toxicity on translocation of the toxin A-chain fi om the endoplasmic reticulum to the cytosol. J Biol Chem 274 34443-34449... 

Figure 5.33 Mechanism of the receptor-mediated induction of CYP1A1 by a polycyclic hydrocarbon such as TCDD. The inducer-receptor (AhR) complex enters the nucleus, binds with ARNT, and the complex binds to the CYP1A1 gene in the DNA. This induces the production of CYP1A1 mRNA, which leads to the production of CYP1A1 protein and functional enzyme. Abbreviations AIP, AhR interacting protein AhR, aryl hydrocarbon receptor HSP, heat shock protein 90 ARNT, AhR nuclear translocator E.R., endoplasmic reticulum.

FIGURE 27-33 Directing eukaryotic proteins with the appropriate signals to the endoplasmic reticulum. This process involves the SRP cycle and translocation and cleavage of the nascent polypeptide. The steps are described in the text. SRP is a rod-shaped complex containing a 300 nucleotide RNA (7SL-RNA) and six different proteins (combined Mr 325,000). One protein subunit of SRP binds directly to... 

The processes by which proteins are selected for secretion into the periplasmic space of bacteria or into the vesicles of the endoplasmic reticulum of eukaryotic cells are similar and have been discussed in Chapter 10 (pp. 519-521). However, some details are still being worked out. The first step in translocation is binding of the N terminus of a protein that is emerging from a ribosome to the signal recognition parti-cje 563,564 j le core 0f this particle has a universally conserved structure consisting of two proteins and an RNA molecule.565 571 b... 

The amber suppressor tRNA (tRNASuP) is introduced to overcome the limitation associated with uniform incorporation of the noncoded amino acid into the target protein. The amino acid-loaded tRNASup incorporates the nonnatural amino acid at a specific site in the protein, corresponding to the nonsense suppression site in the genel144 Phe(4-Tmd)-tRNASup is used to study the interactions of translocating preprolactin with lipids and proteins at the endoplasmic reticulum membranei134 145 ... 

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