Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2.

The Journal of Biological Chemistry
Ida Signe Bohse LarsenAdnan Halim

Abstract

Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1. Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast ...Continue Reading

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Citations

Mar 27, 2018·Glycobiology·Ieva Bagdonaite, Hans H Wandall
Oct 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ida Signe Bohse LarsenAdnan Halim
Sep 13, 2018·Expert Review of Proteomics·Maura Brioschi, Cristina Banfi
May 8, 2020·Molecular Psychiatry·Robert G MealerJordan W Smoller
Jul 9, 2017·The Journal of Biological Chemistry·M Osman Sheikh, Lance Wells
Dec 24, 2018·Disease Models & Mechanisms·Alec R Nickolls, Carsten G Bönnemann
Feb 23, 2021·The Journal of Biological Chemistry·Yoshiki NarimatsuHenrik Clausen
May 25, 2021·Journal of Proteome Research·Mary Luz UribePaul J Hensbergen

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