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Science 14 April 2000:
Vol. 288. no. 5464, pp. 331 - 333
DOI: 10.1126/science.288.5464.331
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Reports

Chaperone Selection During Glycoprotein Translocation into the Endoplasmic Reticulum

Maurizio Molinari, Ari Helenius *

A variety of molecular chaperones and folding enzymes assist the folding of newly synthesized proteins in the endoplasmic reticulum. Here we investigated why some glycoproteins interact with the molecular chaperone BiP, and others with the calnexin/calreticulin pathway. The folding of Semliki forest virus glycoproteins and influenza hemagglutinin was studied in living cells. The initial choice of chaperone depended on the location of N-linked glycans in the growing nascent chain. Direct interaction with calnexin and calreticulin without prior interaction with BiP occurred if glycans were present within about 50 residues of the protein's NH2-terminus.

Swiss Federal Institute of Technology Zurich (ETHZ), Universitätstrasse 16, CH-8092 Zurich, Switzerland.
*   To whom correspondence should be addressed. E-mail: ari.helenius{at}bc.biol.ethz.ch

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C. M. Cabral, Y. Liu, K. W. Moremen, and R. N. Sifers (2002)
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Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER.
M. Molinari, C. Galli, V. Piccaluga, M. Pieren, and P. Paganetti (2002)
J. Cell Biol. 158, 247-257
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Folding and Dimerization of Tick-Borne Encephalitis Virus Envelope Proteins prM and E in the Endoplasmic Reticulum.
I. C. Lorenz, S. L. Allison, F. X. Heinz, and A. Helenius (2002)
J. Virol. 76, 5480-5491
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Folding of Hepatitis C Virus E1 Glycoprotein in a Cell-Free System.
M. Merola, M. Brazzoli, F. Cocchiarella, J. M. Heile, A. Helenius, A. J. Weiner, M. Houghton, and S. Abrignani (2001)
J. Virol. 75, 11205-11217
   Abstract »    Full Text »    PDF »
Relationship between Calnexin and BiP in Suppressing Aggregation and Promoting Refolding of Protein and Glycoprotein Substrates.
V. S. Stronge, Y. Saito, Y. Ihara, and D. B. Williams (2001)
J. Biol. Chem. 276, 39779-39787
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Head-to-tail oligomerization of calsequestrin: a novel mechanism for heterogeneous distribution of endoplasmic reticulum luminal proteins.
G. Gatti, S. Trifari, N. Mesaeli, J.M. R. Parker, M. Michalak, and J. Meldolesi (2001)
J. Cell Biol. 154, 525-534
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Distinct differences in association of MHC class I with endoplasmic reticulum proteins in wild-type, and {beta}2-microglobulin- and TAP-deficient cell lines.
K. M. Paulsson, P. Wang, P. O. Anderson, S. Chen, R. F. Pettersson, and S. Li (2001)
Int. Immunol. 13, 1063-1073
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Intracellular Functions of N-Linked Glycans.
A. Helenius and M. Aebi (2001)
Science 291, 2364-2369
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Mutant Rhodopsin Transgene Expression on a Null Background.
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Invest. Ophthalmol. Vis. Sci. 42, 826-833
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Grp78 Is Involved in Retention of Mutant Low Density Lipoprotein Receptor Protein in the Endoplasmic Reticulum.
M. M. Jorgensen, O. N. Jensen, H. U. Holst, J.-J. Hansen, T. J. Corydon, P. Bross, L. Bolund, and N. Gregersen (2000)
J. Biol. Chem. 275, 33861-33868
   Abstract »    Full Text »    PDF »
Folding and Maturation of Tyrosinase-related Protein-1 Are Regulated by the Post-translational Formation of Disulfide Bonds and by N-Glycan Processing.
G. Negroiu, R. A. Dwek, and S. M. Petrescu (2000)
J. Biol. Chem. 275, 32200-32207
   Abstract »    Full Text »    PDF »
Translation Rate of Human Tyrosinase Determines Its N-Linked Glycosylation Level.
A. Ujvari, R. Aron, T. Eisenhaure, E. Cheng, H. A. Parag, Y. Smicun, R. Halaban, and D. N. Hebert (2001)
J. Biol. Chem. 276, 5924-5931
   Abstract »    Full Text »    PDF »
Glycoprotein Quality Control in the Endoplasmic Reticulum. MANNOSE TRIMMING BY ENDOPLASMIC RETICULUM MANNOSIDASE I TIMES THE PROTEASOMAL DEGRADATION OF UNASSEMBLED IMMUNOGLOBULIN SUBUNITS.
C. Fagioli and R. Sitia (2001)
J. Biol. Chem. 276, 12885-12892
   Abstract »    Full Text »    PDF »
Inhibition of Cytochrome c Release in Fas-mediated Signaling Pathway in Transgenic Mice Induced to Express Hepatitis C Viral Proteins.
K. Machida, K. Tsukiyama-Kohara, E. Seike, S. Tone, F. Shibasaki, M. Shimizu, H. Takahashi, Y. Hayashi, N. Funata, C. Taya, et al. (2001)
J. Biol. Chem. 276, 12140-12146
   Abstract »    Full Text »    PDF »
Role of Extracellular Molecular Chaperones in the Folding of Oxidized Proteins. REFOLDING OF COLLOIDAL THYROGLOBULIN BY PROTEIN DISULFIDE ISOMERASE AND IMMUNOGLOBULIN HEAVY CHAIN-BINDING PROTEIN.
F. Delom, B. Mallet, P. Carayon, and P.-J. Lejeune (2001)
J. Biol. Chem. 276, 21337-21342
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Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates involvement of pre-Golgi intermediates in protein quality control.
C. Zuber, J.-y. Fan, B. Guhl, A. Parodi, J. H. Fessler, C. Parker, and J. Roth (2001)
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