calnexin

Summary

Summary: A lectin found in ENDOPLASMIC RETICULUM membranes that binds to specific N-linked OLIGOSACCHARIDES found on newly synthesized proteins. It may play role in PROTEIN FOLDING or retention and degradation of misfolded proteins in the endoplasmic reticulum.

Top Publications

  1. Molinari M, Galli C, Vanoni O, Arnold S, Kaufman R. Persistent glycoprotein misfolding activates the glucosidase II/UGT1-driven calnexin cycle to delay aggregation and loss of folding competence. Mol Cell. 2005;20:503-12 pubmed
    ..UGT reglucosylation of nonnative glycopolypeptides prevents their release from the calnexin cycle and secretion...
  2. Soldà T, Garbi N, Hämmerling G, Molinari M. Consequences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle. J Biol Chem. 2006;281:6219-26 pubmed
    ..Here we compared maturation of one obligate and two facultative calnexin substrates in cells with and without ERp57, the calnexin-associated, glycoprotein-specific oxidoreductase...
  3. Parodi A. Protein glucosylation and its role in protein folding. Annu Rev Biochem. 2000;69:69-93 pubmed
    ..Recognition of folding glycoproteins by two resident lectins, membrane-bound calnexin and its soluble homolog, calreticulin, is mediated by protein-linked monoglucosylated oligosaccharides...
  4. Denzel A, Molinari M, Trigueros C, Martin J, Velmurgan S, Brown S, et al. Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression. Mol Cell Biol. 2002;22:7398-404 pubmed
    b>Calnexin is a ubiquitously expressed type I membrane protein which is exclusively localized in the endoplasmic reticulum (ER)...
  5. Kang S, Cresswell P. Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain. J Biol Chem. 2002;277:44838-44 pubmed
    ..Here we show that CD1d associates in the ER with both calnexin and calreticulin and with the thiol oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-..
  6. Rosenbaum E, Hardie R, Colley N. Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival. Neuron. 2006;49:229-41 pubmed
    ..Here, we demonstrate a multifunctional role for calnexin as both a molecular chaperone uniquely required for rhodopsin maturation and a regulator of Ca2+ that enters ..
  7. Williams D. Beyond lectins: the calnexin/calreticulin chaperone system of the endoplasmic reticulum. J Cell Sci. 2006;119:615-23 pubmed
    b>Calnexin and calreticulin are related proteins that comprise an ER chaperone system that ensures the proper folding and quality control of newly synthesized glycoproteins...
  8. Schrag J, Bergeron J, Li Y, Borisova S, Hahn M, Thomas D, et al. The Structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell. 2001;8:633-44 pubmed
    The three-dimensional structure of the lumenal domain of the lectin-like chaperone calnexin determined to 2.9 A resolution reveals an extended 140 A arm inserted into a beta sandwich structure characteristic of legume lectins...
  9. Guérin R, Arseneault G, Dumont S, Rokeach L. Calnexin is involved in apoptosis induced by endoplasmic reticulum stress in the fission yeast. Mol Biol Cell. 2008;19:4404-20 pubmed publisher
    ..Mounting evidence indicate that the ER chaperone calnexin is involved in apoptosis caused by ER stress...

More Information

Publications62

  1. Free R, Hazelwood L, Cabrera D, Spalding H, Namkung Y, Rankin M, et al. D1 and D2 dopamine receptor expression is regulated by direct interaction with the chaperone protein calnexin. J Biol Chem. 2007;282:21285-300 pubmed
    ..We have now identified the ER chaperone protein calnexin as an interacting protein for both D(1) and D(2) dopamine receptors...
  2. Danilczyk U, Williams D. The lectin chaperone calnexin utilizes polypeptide-based interactions to associate with many of its substrates in vivo. J Biol Chem. 2001;276:25532-40 pubmed
    b>Calnexin and calreticulin are molecular chaperones of the endoplasmic reticulum that bind to newly synthesized glycoproteins in part through a lectin site specific for monoglucosylated (Glc(1)Man(7-9)GlcNAc(2)) oligosaccharides...
  3. Lakkaraju A, Abrami L, Lemmin T, Blasković S, Kunz B, Kihara A, et al. Palmitoylated calnexin is a key component of the ribosome-translocon complex. EMBO J. 2012;31:1823-35 pubmed publisher
    ..Here, we show that calnexin, a major ER chaperone involved in glycoprotein folding is palmitoylated and that this modification is mediated by ..
  4. Bedard K, Szabo E, Michalak M, Opas M. Cellular functions of endoplasmic reticulum chaperones calreticulin, calnexin, and ERp57. Int Rev Cytol. 2005;245:91-121 pubmed
    ..Calreticulin, calnexin, and ERp57 are among the endoplasmic chaperones that interact with partially folded glycoproteins and determine ..
  5. Farinha C, Amaral M. Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol Cell Biol. 2005;25:5242-52 pubmed
    ..Structural fidelity is monitored by endoplasmic reticulum (ER) quality control involving the molecular chaperone calnexin. Retained misfolded proteins undergo ER-associated degradation (ERAD) through the ubiquitin-proteasome pathway...
  6. Frenkel Z, Shenkman M, Kondratyev M, Lederkremer G. Separate roles and different routing of calnexin and ERp57 in endoplasmic reticulum quality control revealed by interactions with asialoglycoprotein receptor chains. Mol Biol Cell. 2004;15:2133-42 pubmed
    ..ER)p57 interacts with newly synthesized glycoproteins through ternary complexes with the chaperones/lectins calnexin or calreticulin...
  7. Chung J, Lim S, Hong Y, Hwang S, Lee G. Effect of doxycycline-regulated calnexin and calreticulin expression on specific thrombopoietin productivity of recombinant Chinese hamster ovary cells. Biotechnol Bioeng. 2004;85:539-46 pubmed
    ..q(TPO)) of recombinant Chinese hamster ovary (rCHO) cells (CHO-TPO), the effect of expression level of calnexin (CNX) and calreticulin (CRT) on q(TPO) was investigated...
  8. Lee W, Kim K, Singaravelu G, Park B, Kim D, Ahnn J, et al. Alternative chaperone machinery may compensate for calreticulin/calnexin deficiency in Caenorhabditis elegans. Proteomics. 2006;6:1329-39 pubmed
    ..Calreticulin and calnexin are ER resident chaperones well conserved from worm to human...
  9. Kraus A, Groenendyk J, Bedard K, Baldwin T, Krause K, Dubois Dauphin M, et al. Calnexin deficiency leads to dysmyelination. J Biol Chem. 2010;285:18928-38 pubmed publisher
    b>Calnexin is a molecular chaperone and a component of the quality control of the secretory pathway. We have generated calnexin gene-deficient mice (cnx(-/-)) and showed that calnexin deficiency leads to myelinopathy...
  10. Lynes E, Raturi A, Shenkman M, Ortiz Sandoval C, Yap M, Wu J, et al. Palmitoylation is the switch that assigns calnexin to quality control or ER Ca2+ signaling. J Cell Sci. 2013;126:3893-903 pubmed publisher
    The palmitoylation of calnexin serves to enrich calnexin on the mitochondria-associated membrane (MAM)...
  11. Lederkremer G, Glickman M. A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins. Trends Biochem Sci. 2005;30:297-303 pubmed
    ..Although these processes are compartmentalized to either side of the endoplasmic reticulum (ER) membrane, some proteins are sequentially subjected to both because they transverse this membrane for ER-associated degradation. ..
  12. Tomassini B, Malisan F, Franchi L, Nicolò C, Calvo G, Saito T, et al. Calnexin suppresses GD3 synthase-induced apoptosis. FASEB J. 2004;18:1553-5 pubmed
    ..Binding to the molecular chaperone calnexin causes the retention of ST8 within the endoplasmic reticulum (ER) and prevents its relocalization to the Golgi...
  13. Conesa A, Jeenes D, Archer D, van den Hondel C, Punt P. Calnexin overexpression increases manganese peroxidase production in Aspergillus niger. Appl Environ Microbiol. 2002;68:846-51 pubmed
    ..In this work, we analyzed the role of two components of the secretion pathway, the chaperones calnexin and binding protein (BiP), in the production of a fungal peroxidase...
  14. Molinari M, Calanca V, Galli C, Lucca P, Paganetti P. Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle. Science. 2003;299:1397-400 pubmed
    ..EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle...
  15. Oda Y, Hosokawa N, Wada I, Nagata K. EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin. Science. 2003;299:1394-7 pubmed
    ..Here, EDEM was shown to interact with calnexin, but not with calreticulin, through its transmembrane region...
  16. Gassler N, Schnolzer M, Rohr C, Helmke B, Kartenbeck J, Grünewald S, et al. Expression of calnexin reflects paneth cell differentiation and function. Lab Invest. 2002;82:1647-59 pubmed
    ..In this study, we investigated whether calnexin, a protein involved in secretory pathways, might be associated with differentiation and function of Paneth cells ..
  17. Thammavongsa V, Mancino L, Raghavan M. Polypeptide substrate recognition by calnexin requires specific conformations of the calnexin protein. J Biol Chem. 2005;280:33497-505 pubmed
    b>Calnexin is an endoplasmic reticulum chaperone that binds to substrates containing monoglucosylated oligosaccharides. Whether calnexin can also directly recognize polypeptide components of substrates is controversial...
  18. Ireland B, Niggemann M, Williams D. In vitro assays of the functions of calnexin and calreticulin, lectin chaperones of the endoplasmic reticulum. Methods Mol Biol. 2006;347:331-42 pubmed
    b>Calnexin and calreticulin are molecular chaperones of the endoplasmic reticulum (ER) whose folding-promoting functions are directed predominantly toward aspargine-linked glycoproteins...
  19. Delom F, Fessart D, Chevet E. Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells. Apoptosis. 2007;12:293-305 pubmed
    ..Here, we show that tunicamycin causes significant alteration of calnexin sub-cellular distribution in MCF-7 cells...
  20. Morello J, Salahpour A, Petaja Repo U, Laperriere A, Lonergan M, Arthus M, et al. Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry. 2001;40:6766-75 pubmed
    ..Confocal microscopy revealed that they were both retained in the ER. To determine if calnexin could be involved, its interaction with the AVPR2 was assessed...
  21. Wang N, Glidden E, Murphy S, Pearse B, Hebert D. The cotranslational maturation program for the type II membrane glycoprotein influenza neuraminidase. J Biol Chem. 2008;283:33826-37 pubmed publisher
    ..The type II orientation provides experimental advantages to monitor the first maturation steps. Calnexin was shown to cotranslationally interact with NA prior to calreticulin...
  22. Meunier L, Usherwood Y, Chung K, Hendershot L. A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell. 2002;13:4456-69 pubmed
    ..It is noticeable that most of the components of the calnexin/calreticulin system, which include some of the most abundant chaperones inside the ER, are either not detected in ..
  23. Zhang Y, Kozlov G, Pocanschi C, Brockmeier U, Ireland B, Maattanen P, et al. ERp57 does not require interactions with calnexin and calreticulin to promote assembly of class I histocompatibility molecules, and it enhances peptide loading independently of its redox activity. J Biol Chem. 2009;284:10160-73 pubmed publisher
    ..Since ERp57 associates with the lectin chaperones calnexin and calreticulin, it is thought that ERp57 requires these chaperones to gain access to its substrates...
  24. Wanamaker C, Green W. N-linked glycosylation is required for nicotinic receptor assembly but not for subunit associations with calnexin. J Biol Chem. 2005;280:33800-10 pubmed
    ..Because the chaperone calnexin (CN) associates with N-linked glycans, we examined CN interactions with AChR subunits...
  25. Higgins M, Demir M, Tate C. Calnexin co-expression and the use of weaker promoters increase the expression of correctly assembled Shaker potassium channel in insect cells. Biochim Biophys Acta. 2003;1610:124-32 pubmed
    ..In addition, co-expression of the molecular chaperone, calnexin, increased the quantity of correctly assembled channel protein, suggesting that calnexin can be used to increase ..
  26. Noorwez S, Sama R, Kaushal S. Calnexin improves the folding efficiency of mutant rhodopsin in the presence of pharmacological chaperone 11-cis-retinal. J Biol Chem. 2009;284:33333-42 pubmed publisher
    The lectin chaperone calnexin (Cnx) is important for quality control of glycoproteins, and the chances of correct folding of a protein increase the longer the protein interacts with Cnx...
  27. Nouri M, Hiraga S, Yanagawa Y, Sunohara Y, Matsumoto H, Komatsu S. Characterization of calnexin in soybean roots and hypocotyls under osmotic stress. Phytochemistry. 2012;74:20-9 pubmed publisher
    b>Calnexin is an endoplasmic reticulum-localized molecular chaperone protein which is involved in folding and quality control of proteins...
  28. Swanton E, High S, Woodman P. Role of calnexin in the glycan-independent quality control of proteolipid protein. EMBO J. 2003;22:2948-58 pubmed
    ..A glycoprotein-specific system involving the ER lectins calnexin and calreticulin is well documented, but very little is known about mechanisms that may operate for non-..
  29. Ellgaard L, Frickel E. Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding. Cell Biochem Biophys. 2003;39:223-47 pubmed
    ..Essential components of this system include the lectin chaperones calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a glycoprotein specific thiol-disulfide ..
  30. Toyofuku K, Wada I, Spritz R, Hearing V. The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochem J. 2001;355:259-69 pubmed
    ..Pulse-chase experiments showed that all mutant tyrosinases were retained by calnexin in the ER and that they were degraded at similarly rapid rates, which coincided with their dissociation from ..
  31. Brockmeier A, Brockmeier U, Williams D. Distinct contributions of the lectin and arm domains of calnexin to its molecular chaperone function. J Biol Chem. 2009;284:3433-44 pubmed publisher
    b>Calnexin is a Ca2+-binding transmembrane chaperone of the endoplasmic reticulum that recognizes Glc1Man5-9GlcNAc2 oligosaccharides on folding glycoproteins as well as non-native elements of the polypeptide backbone...
  32. Li Q, Su Y, Wang H, Li L, Wang Q, Bao L. Transmembrane segments prevent surface expression of sodium channel Nav1.8 and promote calnexin-dependent channel degradation. J Biol Chem. 2010;285:32977-87 pubmed publisher
    ..Furthermore, co-immunoprecipitation experiments showed that calnexin interacted with acidic amino acid-containing sequences through its transmembrane segment...
  33. Song H, Rohrs H, Tan M, Wohltmann M, Ladenson J, Turk J. Effects of endoplasmic reticulum stress on group VIA phospholipase A2 in beta cells include tyrosine phosphorylation and increased association with calnexin. J Biol Chem. 2010;285:33843-57 pubmed publisher
    ..They include the ER chaperone calnexin, whose association with iPLA(2)? increases upon induction of ER stress...
  34. Turcotte C, Roux A, Beauregard P, Guérin R, Sénéchal P, Hajjar F, et al. The calnexin-independent state does not compensate for all calnexin functions in Schizosaccharomyces pombe. FEMS Yeast Res. 2007;7:196-208 pubmed
    In the yeast Schizosaccharomyces pombe, the molecular chaperone calnexin (Cnx1p) has been shown to be essential for viability. However, we recently reported that, under certain circumstances, S...
  35. Chevet E, Jakob C, Thomas D, Bergeron J. Calnexin family members as modulators of genetic diseases. Semin Cell Dev Biol. 1999;10:473-80 pubmed
    ..In this review we summarize the role of ER resident proteins in quality control of mutated secretory proteins. ..
  36. Hosokawa N, Wada I, Natsuka Y, Nagata K. EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded alpha1-antitrypsin. Genes Cells. 2006;11:465-76 pubmed
    ..Co-expression of NHK with two other ER membrane proteins, calnexin and H(+)/K(+)-ATPase (beta subunit), did not inhibit NHK dimer formation or accelerate NHK ERAD...
  37. Zhang L, Wu G, Tate C, Lookene A, Olivecrona G. Calreticulin promotes folding/dimerization of human lipoprotein lipase expressed in insect cells (sf21). J Biol Chem. 2003;278:29344-51 pubmed
    ..with human molecular chaperones, we found that calreticulin had the most pronounced effects on LPL activity, but calnexin was also effective...
  38. Song Y, Azakami H, Shamima B, He J, Kato A. Different effects of calnexin deletion in Saccharomyces cerevisiae on the secretion of two glycosylated amyloidogenic lysozymes. FEBS Lett. 2002;512:213-7 pubmed
    Both glycosylated amyloidogenic lysozymes I55T/G49N and D66H/G49N were expressed in wild-type and calnexin-disrupted Saccharomyces cerevisiae...
  39. Fuller J, Pitzer J, Godwin U, Albertino M, Machon B, Kearse K, et al. Characterization of the molecular chaperone calnexin in the channel catfish, Ictalurus punctatus, and its association with MHC class II molecules. Dev Comp Immunol. 2004;28:603-17 pubmed publisher
    ..b>Calnexin (CNX) is an ER chaperone that associates with glycoproteins bearing a monoglucosylated N-linked oligosaccharide ..
  40. Paulsson K, Wang P. Chaperones and folding of MHC class I molecules in the endoplasmic reticulum. Biochim Biophys Acta. 2003;1641:1-12 pubmed
    ..This review discusses the early stages of MHC class I maturation regarding BiP and calnexin association, and differences in MHC class I heavy chain (HC) interaction with calnexin and calreticulin are ..
  41. Jessop C, Chakravarthi S, Garbi N, Hämmerling G, Lovell S, Bulleid N. ERp57 is essential for efficient folding of glycoproteins sharing common structural domains. EMBO J. 2007;26:28-40 pubmed
    ..This enzyme has been shown to be associated with both calnexin and calreticulin and, therefore, has been proposed to be a glycoprotein-specific oxidoreductase...
  42. Diedrich G, Bangia N, Pan M, Cresswell P. A role for calnexin in the assembly of the MHC class I loading complex in the endoplasmic reticulum. J Immunol. 2001;166:1703-9 pubmed
    ..complex and provide evidence that after TAP and tapasin associate with each other, the transmembrane chaperone calnexin and ERp57 bind to the TAP-tapasin complex to generate an intermediate...
  43. Ciplys E, Sasnauskas K, Slibinskas R. Overexpression of human calnexin in yeast improves measles surface glycoprotein solubility. FEMS Yeast Res. 2011;11:514-23 pubmed publisher
    ..To improve folding and solubility of viral surface glycoprotein, the genes encoding human ER resident chaperones calnexin, calreticulin, immunoglobin binding protein (BiP), protein disulfide isomerase (PDI) and foldase (ERp57) were ..
  44. Maréchal A, Tanguay P, Callejo M, Guérin R, Boileau G, Rokeach L. Cell viability and secretion of active proteins in Schizosaccharomyces pombe do not require the chaperone function of calnexin. Biochem J. 2004;380:441-8 pubmed
    ..b>Calnexin is a key ER chaperone implicated in the folding, retention and targeting for degradation of proteins that go ..
  45. Pollock S, Kozlov G, Pelletier M, Trempe J, Jansen G, Sitnikov D, et al. Specific interaction of ERp57 and calnexin determined by NMR spectroscopy and an ER two-hybrid system. EMBO J. 2004;23:1020-9 pubmed
    b>Calnexin and ERp57 act cooperatively to ensure a proper folding of proteins in the endoplasmic reticulum (ER). Calnexin contains two domains: a lectin domain and an extended arm termed the P-domain...
  46. Schmidt Arras D, Böhmer A, Markova B, Choudhary C, Serve H, Bohmer F. Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. Mol Cell Biol. 2005;25:3690-703 pubmed
    ..Enhanced complex formation of FLT-3 ITD with the ER-resident chaperone calnexin indicates that its retention in the ER is related to inefficient folding...
  47. Wang B, Han S, Lien L, Chang L. Lentiviral calnexin-modified dendritic cells promote expansion of high-avidity effector T cells with central memory phenotype. Immunology. 2009;128:43-57 pubmed publisher
    ..We report that DCs expressing supraphysiological levels of calnexin, a chaperone protein, via lentiviral gene transfer stimulated the expansion of high-avidity CTLs with increased ..
  48. Beauregard P, Guérin R, Turcotte C, Lindquist S, Rokeach L. A nucleolar protein allows viability in the absence of the essential ER-residing molecular chaperone calnexin. J Cell Sci. 2009;122:1342-51 pubmed publisher
    In fission yeast, the ER-residing molecular chaperone calnexin is normally essential for viability...
  49. Lee W, Lee T, Park B, Chang J, Yu J, Koo H, et al. Caenorhabditis elegans calnexin is N-glycosylated and required for stress response. Biochem Biophys Res Commun. 2005;338:1018-30 pubmed
    b>Calnexin, a type I integral Ca(2+)-binding protein in the endoplasmic reticulum (ER) membrane, has been implicated in various biological functions including chaperone activity, calcium homeostasis, phagocytosis, and ER stress-induced ..
  50. Gagnon E, Duclos S, Rondeau C, Chevet E, Cameron P, Steele Mortimer O, et al. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell. 2002;110:119-31 pubmed
    ..We propose that intracellular pathogens have evolved to adapt and exploit ER-mediated phagocytosis to avoid destruction in host cells. ..
  51. Song Y, Sata J, Saito A, Usui M, Azakami H, Kato A. Effects of calnexin deletion in Saccharomyces cerevisiae on the secretion of glycosylated lysozymes. J Biochem. 2001;130:757-64 pubmed
    Disruption of the calnexin gene in Saccharomyces cerevisiae did not lead to gross effects on the levels of cell growth and secretion of wild-type hen egg white lysozymes (HEWL)...
  52. Müller Taubenberger A, Lupas A, Li H, Ecke M, Simmeth E, Gerisch G. Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis. EMBO J. 2001;20:6772-82 pubmed
    Calreticulin and calnexin are Ca2+-binding proteins with chaperone activity in the endoplasmic reticulum...
  53. Delom F, Chevet E. In vitro mapping of calnexin interaction with ribosomes. Biochem Biophys Res Commun. 2006;341:39-44 pubmed
    b>Calnexin is an endoplasmic reticulum (ER) resident type I integral membrane phosphoprotein. This protein is actively involved in the ER glycoprotein quality control through its luminal domain...