Differential dependence on N-glycosylation of anthrax toxin receptors CMG2 and TEM8

PloS One
Sarah FriebeF Gisou van der Goot

Abstract

ANTXR 1 and 2, also known as TEM8 and CMG2, are two type I membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. Here we have analyzed the importance of N-glycosylation on folding, trafficking and ligand binding of these closely related proteins. We find that TEM8 has a stringent dependence on N-glycosylation. The presence of at least one glycan on each of its two extracellular domains, the vWA and Ig-like domains, is indeed necessary for efficient trafficking to the cell surface. In the absence of any N-linked glycans, TEM8 fails to fold correctly and is recognized by the ER quality control machinery. Expression of N-glycosylation mutants reveals that CMG2 is less vulnerable to sugar loss. The absence of N-linked glycans in one of the extracellular domains indeed has little impact on folding, trafficking or receptor function of the wild type protein expressed in tissue culture cells. N-glycans do, however, seem required in primary fibroblasts from human patients. Here, the presence of N-linked sugars increases the tolerance to mutations in cmg2 causing the rare genetic disease Hyaline Fibromatosis Syndrome. It thus appears that CMG2 gl...Continue Reading

References

Jan 1, 1988·Methods in Enzymology·S H Leppla
Jan 1, 1985·Annual Review of Biochemistry·R Kornfeld, S Kornfeld
Aug 13, 1985·Biochemistry·A L TarentinoT H Plummer
Feb 1, 1996·The Journal of Cell Biology·A A McCracken, J L Brodsky
Oct 1, 1996·Chemistry & Biology·S E O'Connor, B Imperiali
Dec 9, 1998·Nature·S L Rutherford, S Lindquist
Aug 19, 2000·Science·B St CroixK W Kinzler
Feb 24, 2001·Clinical Rheumatology·G KeserE Doğanavşargil
Mar 28, 2001·Science·A Helenius, M Aebi
Feb 28, 2003·The EMBO Journal·Christian HirschHidde L Ploegh
Jun 11, 2004·Annual Review of Biochemistry·Ari Helenius, Markus Aebi
Jul 9, 2004·Journal of the American Chemical Society·Carlos J BosquesBarbara Imperiali
Jul 16, 2004·American Journal of Physiology. Cell Physiology·Teresa M BuckWilliam R Skach
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Samiksha KatiyarWilliam J Lennarz
Feb 8, 2005·Current Opinion in Microbiology·Heather M Scobie, John A T Young
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·G Jonah A RaineyJohn A T Young
Jan 13, 2006·The Journal of Cell Biology·Laurence AbramiF Gisou van der Goot
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Akash NandaDavid L Huso
Mar 3, 2006·Glycobiology·Eranthie Weerapana, Barbara Imperiali
Sep 9, 2006·Cell·Kazuaki Ohtsubo, Jamey D Marth
Apr 3, 2007·Trends in Microbiology·David J Vigerust, Virginia L Shepherd
Nov 3, 2007·The Journal of Biological Chemistry·Shihui LiuStephen H Leppla
Feb 28, 2008·The Journal of Biological Chemistry·Julio J Caramelo, Armando J Parodi
Oct 22, 2008·Nature Methods·Rinkoo D Gupta, Dan S Tawfik
Nov 13, 2008·Nature Reviews. Molecular Cell Biology·Shruthi S Vembar, Jeffrey L Brodsky
Dec 30, 2008·Molecular Cell·Erin M QuanJonathan S Weissman
Jan 20, 2009·Bioinformatics·Andrew M WaterhouseGeoffrey J Barton
Jun 6, 2009·Nature·Nobuhiko Tokuriki, Dan S Tawfik
Jul 18, 2009·Journal of Immunotherapy·Zhihua RuanYuzhang Wu
Aug 27, 2009·FEBS Letters·Darren M HuttWilliam E Balch
Oct 3, 2009·Protein Expression and Purification·V AndrianovM Golovkin
Mar 12, 2010·PLoS Pathogens·Laurence AbramiF Gisou van der Goot

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Methods Mentioned

BETA
glycosylation
protein folding
ubiquitination
transfection

Software Mentioned

Zen
FIJI
BioID
Adobe Illustrator
Jalview
Image Quant TL
Typhoon
UCSF Chimera package

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