Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain.

The Journal of Biological Chemistry
C A DwyerRussell T Matthews

Abstract

Protein O-mannosylation is a glycan modification that is required for normal nervous system development and function. Mutations in genes involved in protein O-mannosyl glycosylation give rise to a group of neurodevelopmental disorders known as congenital muscular dystrophies (CMDs) with associated CNS abnormalities. Our previous work demonstrated that receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan is hypoglycosylated in a mouse model of one of these CMDs, known as muscle-eye-brain disease, a disorder that is caused by loss of an enzyme (protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1) that modifies O-mannosyl glycans. In addition, monoclonal antibodies Cat-315 and 3F8 were demonstrated to detect O-mannosyl glycan modifications on RPTPζ/phosphacan. Here, we show that O-mannosyl glycan epitopes recognized by these antibodies define biochemically distinct glycoforms of RPTPζ/phosphacan and that these glycoforms differentially decorate the surface of distinct populations of neural cells. To provide a further structural basis for immunochemically based glycoform differences, we characterized the O-linked glycan heterogeneity of RPTPζ/phosphacan in the early postnatal mouse brain by multidimensional mass spectro...Continue Reading

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Citations

Jan 20, 2017·Glycoconjugate Journal·L DjerbalJcf Kwok
Apr 13, 2018·International Journal of Molecular Sciences·Sian F Irvine, Jessica C F Kwok
May 29, 2018·Angewandte Chemie·Caicai MengHongzhi Cao
Jul 3, 2019·Nature Reviews. Neuroscience·James W FawcettTommaso Pizzorusso
Dec 12, 2019·The Journal of Biological Chemistry·Geoffrey J EillRussell T Matthews
Jan 16, 2020·International Journal of Molecular Sciences·Masamichi NagaeYasuhiko Kizuka
Dec 3, 2017·Disease Models & Mechanisms·Hatylas AzevedoCarlos Alberto Moreira-Filho
May 11, 2018·Journal of the American Society for Mass Spectrometry·John D BenktanderMilos V Novotny
Nov 19, 2019·Journal of the American Chemical Society·Tian GaoHongzhi Cao

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