Glycans of myelin proteins

Abstract

Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn(93) , the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn(36) , MOG at Asn(31) ), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N-acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T(95) →M is a very common in Europe and is associated with a late-onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study.

Structural basis of myelin-associated glycoprotein adhesion and signalling

“…8). The other glycans are not expected to interfere with dimerization, also not when considering myelin-specific N-linked glycans37. We confirmed that MAG dimerizes in solution via the Ig4–Ig5 interface by analysing glycosylated and deglycosylated forms of MAG 1–5 , MAG 1–3 (that lacks the dimerization domains) and the aforementioned mutants in small angle X-ray scattering (SAXS) and AUC experiments.…”

Myelin extracellular leaflet compaction requires apolipoprotein D membrane management to optimize lysosomal‐dependent recycling and glycocalyx removal

“…Since no alterations are observed in the content of the abundant glycoprotein Mag (Figure ), which is highly sialylated (Sedzik, Jastrzebski, & Grandis, ), we studied the most sialylated species of gangliosides in the nervous system (Gong et al, ; Lunn et al, ; Vajn, Viljetic, Degmecic, Schnaar, & Heffer, ). We used antibodies specific for GM1–2b and GD1a (belonging to the A‐series of ganglioside biosynthesis, with 1 and 2 sialic acid moieties), and for GD1b and GT1b (from the B‐series, with 2 and 3 sialic acid residues).…”

The leptin receptor mutation of the obese Zucker rat causes sciatic nerve demyelination with a centripetal pattern defect

“…[1][2][3][4][5][6]87,88 In PNS myelin, among all its non-phospholipid metabolome, large amounts of PGs or plasmalogens contribute to its architecture, integrity of adherence of the neuroplasm, and to nerve protection and insulation. [150][151][152][153][154] Further, the neuroplasm interacts with myelin both ways [155][156][157][158][159] , with cadherins [160][161][162][163][164][165][166] and others still to be found [165][166][167][168] as well as to place periaxin 169 with connexin 32 (Cx32). 170 The alignment and points of adherence of the defects can suggest one of the most abundant myelin PGs involved, such as myelin protein zero (P0) which core integral protein replaces the proteolipid protein or PLP found in the CNS myelin.…”