Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates.
Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have be...
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Public Library of Science (PLoS)
2016-01-01
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Online Access: | http://europepmc.org/articles/PMC5094735?pdf=render |
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author | Markus F Bartels Patrick R Winterhalter Jin Yu Yan Liu Mark Lommel Frank Möhrlen Huaiyu Hu Ten Feizi Ulrika Westerlind Thomas Ruppert Sabine Strahl |
author_facet | Markus F Bartels Patrick R Winterhalter Jin Yu Yan Liu Mark Lommel Frank Möhrlen Huaiyu Hu Ten Feizi Ulrika Westerlind Thomas Ruppert Sabine Strahl |
author_sort | Markus F Bartels |
collection | DOAJ |
description | Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. |
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language | English |
last_indexed | 2024-12-22T20:36:57Z |
publishDate | 2016-01-01 |
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spelling | doaj.art-0e55cae37ad34da6ad472d953ef1ffdc2022-12-21T18:13:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011111e016611910.1371/journal.pone.0166119Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates.Markus F BartelsPatrick R WinterhalterJin YuYan LiuMark LommelFrank MöhrlenHuaiyu HuTen FeiziUlrika WesterlindThomas RuppertSabine StrahlProtein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins.http://europepmc.org/articles/PMC5094735?pdf=render |
spellingShingle | Markus F Bartels Patrick R Winterhalter Jin Yu Yan Liu Mark Lommel Frank Möhrlen Huaiyu Hu Ten Feizi Ulrika Westerlind Thomas Ruppert Sabine Strahl Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. PLoS ONE |
title | Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. |
title_full | Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. |
title_fullStr | Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. |
title_full_unstemmed | Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. |
title_short | Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. |
title_sort | protein o mannosylation in the murine brain occurrence of mono o mannosyl glycans and identification of new substrates |
url | http://europepmc.org/articles/PMC5094735?pdf=render |
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