Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS.
The CNS-restricted versican splice-variant V2 is a large chondroitin sulfate proteoglycan incorporated in the extracellular matrix surrounding myelinated fibers and particularly accumulating at nodes of Ranvier. In vitro, it is a potent inhibitor of axonal growth and therefore considered to participate in the reduction of structural plasticity connected to myelination. To study the role of versican V2 during postnatal development, we designed a novel isoform-specific gene inactivation approach circumventing early embryonic lethality of the complete knock-out and preventing compensation by the remaining versican splice variants. These mice are viable and fertile; however, they display major molecular alterations at the nodes of Ranvier. While the clustering of nodal sodium channels and paranodal structures appear in versican V2-deficient mice unaffected, the formation of the extracellular matrix surrounding the nodes is largely impaired. The conjoint loss of tenascin-R and phosphacan from the perinodal matrix provide strong evidence that versican V2, possibly controlled by a nodal receptor, organizes the extracellular matrix assembly in vivo.
Dours-Zimmermann
María T
MT
Institutes of Surgical Pathology and Anesthesiology, University Hospital Zurich, CH-8091 Zurich, Switzerland.
Maurer
Konrad
K
Rauch
Uwe
U
Stoffel
Wilhelm
W
Fässler
Reinhard
R
Zimmermann
Dieter R
DR
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology*; D058966:Contactins; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D051663:Kv1.2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D053675:Versicans / Q000145:classification / Q000172:deficiency / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D051663:Kv1.2 Potassium Channel; D004676:Myelin Basic Protein; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D019063:Tenascin; D053675:Versicans; C074638:tenascin R; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5