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Neurochemical Research

, Volume 38, Issue 12, pp 2490–2502 | Cite as

Nfasc155H and MAG are Specifically Susceptible to Detergent Extraction in the Absence of the Myelin Sphingolipid Sulfatide

  • A. D. Pomicter
  • J. M. DeLoyht
  • A. R. Hackett
  • N. Purdie
  • C. Sato-Bigbee
  • S. C. Henderson
  • J. L. Dupree
Original Paper

Abstract

Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that deteriorate with age. Similar instability also occurs in mice that lack contactin, contactin-associated protein or neurofascin155 (Nfasc155), the proteins that cluster in the paranode and form the junctional complex that mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not been shown to be enriched in the paranode nor has a sulfatide paranodal binding partner been identified; thus, it remains unclear how the absence of sulfatide results in compromised paranode integrity. Using an in situ extraction procedure, it has been reported that the absence of the myelin sphingolipids, galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to detergent extraction. Here, employing a similar approach, we demonstrate that in the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is susceptible to detergent extraction. Furthermore, we use this in situ approach to show that stable association of myelin-associated glycoprotein (MAG) with the myelin membrane is sulfatide dependent while the membrane associations of myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide phosphodiesterase are sulfatide independent. These findings indicate that myelin proteins maintain their membrane associations by different mechanisms. Moreover, the myelin proteins that cluster in the paranode and require sulfatide mediate myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for maintaining Nfasc155 and MAG associations is intriguing since the fatty acid composition of sulfatide is altered and paranodal ultrastructure is compromised in multiple sclerosis. Thus, our findings present a potential link between sulfatide perturbation and myelin deterioration in multiple sclerosis.

Keywords

Sulfatide Neurofascin Membrane rafts Myelin 

Notes

Acknowledgments

The authors wish to thank Drs. Manzoor Bhat, Peter Brophy, and Matt Rasband for their generous gifts of antibodies. This work was funded by a grant from the National Institute of Health-National Institute of Neurologic Disease and Stroke (R03 NS066186 (JLD)). All microscopy was performed at the VCU Department of Anatomy and Neurobiology Microscopy Facility, supported, in part, with funding from an National Institute of Health Center core grant (5P30NS047463).

Conflict of interest

The authors report no conflict of interests.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • A. D. Pomicter
    • 1
  • J. M. DeLoyht
    • 1
    • 2
  • A. R. Hackett
    • 1
  • N. Purdie
    • 1
  • C. Sato-Bigbee
    • 3
  • S. C. Henderson
    • 1
  • J. L. Dupree
    • 1
  1. 1.Department of Anatomy and NeurobiologyVirginia Commonwealth UniversityRichmondUSA
  2. 2.Department of Neuroscience CurriculumVirginia Commonwealth UniversityRichmondUSA
  3. 3.Department of Biochemistry and Molecular BiologyVirginia Commonwealth UniversityRichmondUSA

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