Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates.
2016
Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe
congenital muscular dystrophiesoften 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
mannosealso 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-
mannoseresidues. Among the candidates identified are members of the cadherin and
plexinsuperfamilies and the perineural net protein
neurocan. In addition, we identified
neurexin3, a
cell adhesion proteininvolved in synaptic plasticity, and
inter-alpha-trypsin inhibitor5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins.
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