Protein O-Mannosylation in the murine brain

• Verfasst von: Bartels, Markus F. [VerfasserIn]
• Verfasst von: Winterhalter, Patrick R. [VerfasserIn]
• Verfasst von: Lommel, Mark [VerfasserIn]
• Verfasst von: Möhrlen, Frank [VerfasserIn]
• Verfasst von: Strahl, Sabine [VerfasserIn]
• Titel: Protein O-Mannosylation in the murine brain
• Titelzusatz: occurrence of Mono-O-Mannosyl glycans and identification of new substrates
• Verf.angabe: Markus F. Bartels, Patrick R. Winterhalter, Jin Yu, Yan Liu, Mark Lommel, Frank Möhrlen, Huaiyu Hu, Ten Feizi, Ulrika Westerlind, Thomas Ruppert, Sabine Strahl
• Fussnoten: Gesehen am 04.05.2017
• Titel Quelle: Enthalten in: Public Library of Science: PLoS one
• Jahr Quelle: 2016
• Band/Heft Quelle: 11(2016,11) Artikel-Nummer e0166119, 23 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0166119
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1557914141

Abstract

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.