Oligodendrocyte Myelin Glycoprotein Does Not Influence Node of Ranvier Structure or Assembly

Program in Developmental Biology and Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2010; 30(43):14476-81. DOI: 10.1523/JNEUROSCI.1698-10.2010
Source: PubMed


Oligodendrocyte myelin glycoprotein (OMgp) is expressed by both neurons and oligodendrocytes in the CNS. It has been implicated in growth cone collapse and neurite outgrowth inhibition by signaling through the Nogo receptor and paired Ig-like receptor B (PirB). OMgp was also reported to be an extracellular matrix (ECM) protein surrounding CNS nodes of Ranvier and proposed to function as (1) an inhibitor of nodal collateral sprouting and (2) an important contributor to proper nodal and paranodal architecture. However, we show here that the anti-OMgp antiserum used in previous studies to define the functions of OMgp at nodes is not specific. Among all reported nodal ECM components, the antiserum exhibited strong cross-reactivity against versican V2 isoform, a chondroitin sulfate proteoglycan. Furthermore, the OMgp antiserum labeled OMgp-null nodes, but not nodes from versican V2-deficient mice, and preadsorption of the OMgp antiserum with recombinant versican V2 blocked nodal labeling. Analysis of CNS nodes in OMgp-null mice failed to reveal any nodal or paranodal defects, or increased nodal collateral sprouting, indicating that OMgp does not participate in CNS node of Ranvier assembly or maintenance. We successfully identified a highly specific anti-OMgp antibody and observed OMgp staining in white matter only after initiation of myelination. OMgp immunoreactivity decorated the surface of mature myelinated axons, but was excluded from compact myelin and nodes. Together, our results strongly argue against the nodal localization of OMgp and its proposed functions at nodes, and reveal OMgp's authentic localization relative to nodes and myelin.

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Available from: Kae-Jiun Chang, Dec 12, 2013
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    • "OMgp has been implicated in the restriction of axonal regeneration by signaling through the Nogo receptor and PirB (see below) and it may prevent axons from collateral sprouting (Chang et al., 2010; Huang et al., 2005). In previous reports, OMgp expression was initially observed in oligodendrocytes in the CNS and later it was also detected on the surface of several neuronal cell types (Huang et al., 2012; 2005; Habib et al., 1998). "
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    ABSTRACT: Purpose: When central nervous system axons are injured, regeneration is partly inhibited by myelin-associated inhibitors (MAIs). Following traumatic brain injury (TBI) in the rat, pharmacological neutralisation of the MAIs Nogo-A and myelin-associated glycoprotein (MAG) resulted in improved functional outcome. In contrast, genetic or pharmacological neutralization of the MAI receptors Nogo-66 receptor 1 (NgR1) or paired-immunoglobulin like receptor-B (PirB) showed an unaltered or impaired outcome following TBI in mice. The aim of the present study was thus to evaluate the MAI expression levels following TBI in mice. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure total RNA isolated from brains of young adult male C57BL/6 mice at one, three or seven days following controlled cortical impact TBI or sham injury. Hippocampal and neocortical tissue ipsi- and contralateral to the injury was analyzed for Nogo-A, oligodendrocyte-myelin glycoprotein (OMgp), MAG, and the MAI receptors PirB and NgR1, including its co-receptor Lingo1. Results: Compared to sham-injured controls, PirB neocortical expression was significantly upregulated at one day and NgR1 expression downregulated at seven days post-TBI. In the hippocampus, transcriptional upregulation was observed in Nogo-A (one day post-injury), MAG and PirB at seven days post-injury. In contrast, the hippocampal transcripts of NgR1 and Lingo1 were decreased at seven days post-injury. The expression of OMgp was unaltered at all time points post-injury. Conclusion: These results suggest that early dynamic changes in MAI gene expression occur following TBI in the mouse, particularly in the hippocampus, which may play an inhibitory role for post-injury regeneration and plasticity.
    Full-text · Article · Jul 2014 · Restorative neurology and neuroscience
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    • "Huang et al (2005) initially reported an interesting physiological role of OMgp, which was to inhibit aberrant collateral sprouting from the nodes of Ranvier through its expression in oligodendroglia-like cells that ensheath the nodes during development. However, a more recent study disputes this phenotype and attributes the reported nodeensheathing OMgp immunoreactivity to cross reactivity of the antibodies used with versican V2 (Chang, et al., 2010). Thus, the physiological role of OMgp in developmental axon sprouting remains to be fully understood. "
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    ABSTRACT: Myelin-associated inhibitors of axon growth, including Nogo, MAG and OMgp, have been the subject of intense research. A myriad of experimental approaches have been applied to investigate the potential of targeting these molecules to promote axonal repair after spinal cord injury. However, there are still conflicting results on their role in axon regeneration and therefore a lack of a cohesive mechanism on how these molecules can be targeted to promote axon repair. One major reason may be the lack of a clear definition of axon regeneration in the first place. Nevertheless, recent data from genetic studies in mice indicate that the roles of these molecules in CNS axon repair may be more intricate than previously envisioned.
    Full-text · Article · May 2011 · Experimental Neurology
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