Novel forms of neurofascin 155 in the central nervous system: Alterations in paranodal disruption models and multiple sclerosis

Anthony D. Pomicter, Seema M. Shroff, Babette Fuss, Carmen Sato-Bigbee, Peter J. Brophy, Matthew N. Rasband, Manzoor Bhat, Jeffrey L. Dupree

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Stability of the myelin-axon unit is achieved, at least in part, by specialized paranodal junctions comprised of the neuronal heterocomplex of contactin and contactin-associated protein and the myelin protein neurofascin 155. In multiple sclerosis, normal distribution of these proteins is altered, resulting in the loss of the insulating myelin and consequently causing axonal dysfunction. Previously, this laboratory reported that mice lacking the myelin-enriched lipid sulphatide are characterized by a progressive deterioration of the paranodal structure. Here, it is shown that this deterioration is preceded by significant loss of neurofascin 155 clustering at the myelin paranode. Interestingly, prolonged electrophoretic separation revealed the existence of two neurofascin 155 bands, neurofascin 155 high and neurofascin 155 low, which are readily observed following N-linked deglycosylation. Neurofascin 155 high is observed at 7 days of age and reaches peak expression at one month of age, while neurofascin 155 low is first observed at 14 days of age and constantly increases until 5 months of age. Studies using conditional neurofascin knockout mice indicated that neurofascin 155 high and neurofascin 155 low are products of the neurofascin gene and are exclusively expressed by oligodendrocytes within the central nervous system. Neurofascin 155 high is a myelin paranodal protein while the distribution of neurofascin 155 low remains to be determined. While neurofascin 155 high levels are significantly reduced in the sulphatide null mice at 15 days, 30 days and 4 months of age, neurofascin 155 low levels remain unaltered. Although maintained at normal levels, neurofascin 155 low is incapable of preserving paranodal structure, thus indicating that neurofascin 155 high is required for paranodal stability. Additionally, comparisons between neurofascin 155 high and neurofascin 155 low in human samples revealed a significant alteration, specifically in multiple sclerosis plaques.

Original languageEnglish (US)
Pages (from-to)389-405
Number of pages17
JournalBrain
Volume133
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Fingerprint

Myelin Sheath
Multiple Sclerosis
Contactins
Central Nervous System
Sulfoglycosphingolipids
Myelin Proteins
Normal Distribution
Oligodendroglia
Knockout Mice
Cluster Analysis
Axons
Proteins
Lipids
Genes

Keywords

  • Caspr
  • Cerebroside sulphotransferase
  • Myelin
  • Paranode
  • Sulphatide

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Pomicter, A. D., Shroff, S. M., Fuss, B., Sato-Bigbee, C., Brophy, P. J., Rasband, M. N., ... Dupree, J. L. (2010). Novel forms of neurofascin 155 in the central nervous system: Alterations in paranodal disruption models and multiple sclerosis. Brain, 133(2), 389-405. https://doi.org/10.1093/brain/awp341

Novel forms of neurofascin 155 in the central nervous system : Alterations in paranodal disruption models and multiple sclerosis. / Pomicter, Anthony D.; Shroff, Seema M.; Fuss, Babette; Sato-Bigbee, Carmen; Brophy, Peter J.; Rasband, Matthew N.; Bhat, Manzoor; Dupree, Jeffrey L.

In: Brain, Vol. 133, No. 2, 02.2010, p. 389-405.

Research output: Contribution to journalArticle

Pomicter, AD, Shroff, SM, Fuss, B, Sato-Bigbee, C, Brophy, PJ, Rasband, MN, Bhat, M & Dupree, JL 2010, 'Novel forms of neurofascin 155 in the central nervous system: Alterations in paranodal disruption models and multiple sclerosis', Brain, vol. 133, no. 2, pp. 389-405. https://doi.org/10.1093/brain/awp341
Pomicter, Anthony D. ; Shroff, Seema M. ; Fuss, Babette ; Sato-Bigbee, Carmen ; Brophy, Peter J. ; Rasband, Matthew N. ; Bhat, Manzoor ; Dupree, Jeffrey L. / Novel forms of neurofascin 155 in the central nervous system : Alterations in paranodal disruption models and multiple sclerosis. In: Brain. 2010 ; Vol. 133, No. 2. pp. 389-405.
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