Oligodendrocyte myelin glycoprotein does not influence node of ranvier structure or assembly.
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.
Chang
Kae-Jiun
KJ
Program in Developmental Biology and Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Susuki
Keiichiro
K
Dours-Zimmermann
Maria T
MT
Zimmermann
Dieter R
DR
Rasband
Matthew N
MN
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000918:Antibody Specificity; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D015153:Blotting, Western; D003429:Cross Reactions; D005109:Extracellular Matrix / Q000502:physiology; D058851:GPI-Linked Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D004856:Postural Balance / Q000235:genetics / Q000502:physiology; D011901:Ranvier's Nodes / Q000235:genetics / Q000502:physiology*; D053675:Versicans / Q000235:genetics / Q000502:physiology
D019138:Antibodies, Blocking; D058851:GPI-Linked Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C560529:Omg protein, mouse; D053675:Versicans