Calnexin

Affect folding of certain proteins Calnexin,calreticulin... 

Proteins translated on the RER generally fold and assemble into subimits in the ER before being transferred to the Golgi apparatus. Other proteins fold in the cytoplasm. Molecular chaperones (proteins such as calnexin and BiP) assist in this process of protein folding. Proteins that are misfolded are targeted for destruction by ubiquitin and digested in cytoplasmic protein-digesting complexes called proteasomes. 

Keller SH, Lindstrom J, Taylor P (1998) Inhibition of glucose trimming with castano-spermine reduces calnexin assodation and promotes proteasome degradation of the a-subunit of the nicotinic acetylcholine receptor. J Biol Chem 273 17064-17072... 

Mayer TU, Braun T, Jentsch, S (1998) Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein. EMBO ] 17 3251-3257 McCracken AA, Brodsky JL (1996) Assembly of ER-associated protein degradation in vitro dependence on cytosol, calnexin, and ATP. J Cell Biol 132 291-298 McDonald HB, Byers B (1997) A proteasome cap subunit required for spindle pole body duplication in yeast. J Cell Biol 137 539-553 McGee TP, Cheng HH, Kumagai H, Omura S, Simoni RD (1996) Degradation of 3-hydroxy-3-methylg utaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis. J Biol Chem 271 25630-25638... 

SERCA pumps sequester Ca2+ in the ER lumen By maintaining appropriate Ca2+ concentrations in the ER lumen, SERCA pumps also play an essential role in protein synthesis, folding and transport of membrane and secreted proteins. This involves in particular chaperone-dependent processing and post-translational modifications which require a unique calcium rich environment. Chaperone molecules such as calreticulin and calnexin are involved in the quality control pathway in the ER (Berridge, 2002 Ellgaard and Helenius, 2003 Michalak et al., 2002). 

Roderick, H. L., Lechleiter, J. D., and Camacho, P., 2000, Cytosolic phosphorylation of calnexin controls intracellular Ca(2+) oscillations via an interaction with SERCA2b. J Cell Biol, 149 1235 18. 

McCool D.J., Okada Y., Forstner J.F. and Forstner G.G. (1999) Roles of calreticulin and calnexin during mucin synthesis in LSI80 and HT29/A1 human colonic adenocarcinoma cells. Biochem J 341, 593-600... 

Hasenfratz, M.P., Jeltsch, J.M., Michalak, M., and Durst, F., Cloning and characterization of a wounding-induced analog of the chaperone calnexin from Helianthus tuberosus, Plant Physiol. Biochem., 35, 553-564, 1997. 

Calnexin and its soluble homologous calreticulin belong to the family of lectinlike chaperones. Their task is to interact with the partially trimmed monoglycosy-lated N-linked oligosaccharides and therefore contribute to an important part of the maturation and quality control mechanisms of glycoproteins [72]. The expression... 

Calnexin Chaperone, Fectin Folding of glycoproteins clxA... 

Conesa A, Jeenes D, Archer DB et al (2002) Calnexin overexpression increases manganese peroxidase production in Aspergillus niger. Appl Environ Microbiol 68 846-851... 

Helenius A, Trombetta ES, Hebert DN et al (1997) Calnexin, calreticulin and the folding of glycoproteins. Trends Cell Biol 7 193-200... 

Nauseef WM, McCormick SJ, Goedken M (1998) Coordinated participation of calreticulin and calnexin in the biosynthesis of myeloperoxidase. J Biol Chem 273 7107-7111... 

An alternative hypothesis is that ER retention of Z-a,-anti trypsin results in autophagy, specifically of hepatic mitochondria. The basis for this hypothesis is the increase in autophagosomes in cells engineered for inducible expression of Z-tx,-antitrypsin. The mutant protein, along with the chaperone molecule calnexin, can be found in these autophagosomes by immune electron microscopy. It is postulated that mitochondrial dysfunction results from the damage to the mitochondria in the PIZZ liver, leading to the hepatic injury. 

---