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...

Full description

Bibliographic Details
Main Authors: Markus F Bartels, Patrick R Winterhalter, Jin Yu, Yan Liu, Mark Lommel, Frank Möhrlen, Huaiyu Hu, Ten Feizi, Ulrika Westerlind, Thomas Ruppert, Sabine Strahl
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5094735?pdf=render
_version_ 1819174311413415936
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.
first_indexed 2024-12-22T20:36:57Z
format Article
id doaj.art-0e55cae37ad34da6ad472d953ef1ffdc
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-22T20:36:57Z
publishDate 2016-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
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
work_keys_str_mv AT markusfbartels proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT patrickrwinterhalter proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT jinyu proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT yanliu proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT marklommel proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT frankmohrlen proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT huaiyuhu proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT tenfeizi proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT ulrikawesterlind proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT thomasruppert proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates
AT sabinestrahl proteinomannosylationinthemurinebrainoccurrenceofmonoomannosylglycansandidentificationofnewsubstrates