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A novel myelin basic protein transcript variant in the murine central nervous system

  • Anddre Osmar Valdivia
  • Valentina Farr
  • Sanjoy K. BhattacharyaEmail author
Short Communication

Abstract

Myelin basic protein is a multifunctional protein whose primary role is to adhere membranes of the myelin sheath. There are various isoforms that have been identified, 6 distinct isoforms in human and 13 distinct isoforms in mice. These distinct isoforms are the product of alternative splicing of a single gene. The present study sought out to identify the different isoforms found in the murine central nervous system. Neuronal tissue (brain) from five different C57BL6/J mice at 2 months of age was harvested and used for mRNA extraction. mRNA was reversed transcribed to cDNA and transcripts were detected through PCR amplification and DNA agarose gel separation. Primers for exon 1, exon 5b and exon 11 of the myelin basic protein gene were used to capture all the possible transcripts that are naturally found in the murine central nervous system. Unknown transcript was sequenced at Genewiz facilities (South Plainfield, NJ) and mass spectrometry protein sequence analysis demonstrated the presence of a novel myelin basic protein transcript variant. We identified a novel transcript variant of myelin basic protein. This novel transcript variant corresponds to a myelin basic protein of 32.5 kDa which has not been previously reported. This novel transcript variant presents relevant clinical significance to various demyelinating diseases due to its contribution to the understanding of the natural state of the murine central nervous system.

Keywords

Myelin basic protein Transcript variant Myelin sheath Central nervous system Golli myelin basic protein 

Notes

Acknowledgements

This work was supported by an unrestricted grant to the University of Miami from Research to Prevent Blindness (RPB), Department of Defense Grant WHX81-16-0715 and NIH Grant EY027257.

References

  1. 1.
    Hartline DK, Colman DR (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Curr Biol 17(1):R29–R35.  https://doi.org/10.1016/j.cub.2006.11.042 CrossRefGoogle Scholar
  2. 2.
    Jahn O, Tenzer S, Werner H (2009) Myelin proteomics: molecular anatomy of an insulating sheath. Mol Neurobiol 40(1):55–72.  https://doi.org/10.1007/s12035-009-8071-2 CrossRefGoogle Scholar
  3. 3.
    Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81(2):871–927.  https://doi.org/10.1152/physrev.2001.81.2.871 CrossRefGoogle Scholar
  4. 4.
    Kramer EM, Schardt A, Nave KA (2001) Membrane traffic in myelinating oligodendrocytes. Microsc Res Tech 52(6):656–671.  https://doi.org/10.1002/jemt.1050 CrossRefGoogle Scholar
  5. 5.
    Moscarello MA, Wood DD, Boulias C, Ackerley C (1994) Myelin in multiple sclerosis is developmentally immature. J Clin Investig 94(1):146–154.  https://doi.org/10.1172/JCI117300 CrossRefGoogle Scholar
  6. 6.
    Kursula P (2008) Structural properties of proteins specific to the myelin sheath. Amino Acids 34(2):175–185.  https://doi.org/10.1007/s00726-006-0479-7 CrossRefGoogle Scholar
  7. 7.
    Boggs JM (2008) Myelin basic protein. Nova Science Publishers, Incorporated, New YorkGoogle Scholar
  8. 8.
    Boggs JM (2006) Myelin basic protein: a multifunctional protein. Cell Mol Life Sci CMLS 63(17):1945–1961.  https://doi.org/10.1007/s00018-006-6094-7 CrossRefGoogle Scholar
  9. 9.
    Harauz G, Ishiyama N, Hill CM, Bates IR, Libich DS, Fares C (2004) Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis. Micron (Oxford, England: 1993) 35(7):503–542.  https://doi.org/10.1016/j.micron.2004.04.005 CrossRefGoogle Scholar
  10. 10.
    Feng JM, Fernandes AO, Campagnoni CW, Hu YH, Campagnoni AT (2004) The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes. J Neuroimmunol 152(1–2):57–66.  https://doi.org/10.1016/j.jneuroim.2004.03.021 CrossRefGoogle Scholar
  11. 11.
    Min Y, Kristiansen K, Boggs JM, Husted C, Zasadzinski JA, Israelachvili J (2009) Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein. Proc Natl Acad Sci USA 106(9):3154.  https://doi.org/10.1073/pnas.0813110106 CrossRefGoogle Scholar
  12. 12.
    Pedraza L, Fidler L, Staugaitis SM, Colman DR (1997) The active transport of myelin basic protein into the nucleus suggests a regulatory role in myelination. Neuron 18(4):579–589CrossRefGoogle Scholar
  13. 13.
    Staugaitis SM, Colman DR, Pedraza L (1996) Membrane adhesion and other functions for the myelin basic proteins. Bioessays 18(1):13–18.  https://doi.org/10.1002/bies.950180106 CrossRefGoogle Scholar
  14. 14.
    Dyer CA, Philibotte TM, Billings-Gagliardi S, Wolf MK (1995) Cytoskeleton in myelin-basic-protein-deficient shiverer oligodendrocytes. Dev Neurosci 17(1):53–62.  https://doi.org/10.1159/000111273 CrossRefGoogle Scholar
  15. 15.
    Dyer CA (2002) The structure and function of myelin: from inert membrane to perfusion pump. Neurochem Res 27(11):1279–1292CrossRefGoogle Scholar
  16. 16.
    Boggs JM, Rangaraj G (2000) Interaction of lipid-bound myelin basic protein with actin filaments and calmodulin. Biochemistry 39(26):7799–7806CrossRefGoogle Scholar
  17. 17.
    Libich DS, Hill CM, Bates IR, Hallett FR, Armstrong S, Siemiarczuk A, Harauz G (2003) Interaction of the 18.5-kD isoform of myelin basic protein with Ca2+-calmodulin: effects of deimination assessed by intrinsic Trp fluorescence spectroscopy, dynamic light scattering, and circular dichroism. Protein Sci 12(7):1507–1521.  https://doi.org/10.1110/ps.0303603 CrossRefGoogle Scholar
  18. 18.
    Boggs JM, Rangaraj G, Hill CM, Bates IR, Heng YM, Harauz G (2005) Effect of arginine loss in myelin basic protein, as occurs in its deiminated charge isoform, on mediation of actin polymerization and actin binding to a lipid membrane in vitro. Biochemistry 44(9):3524–3534.  https://doi.org/10.1021/bi0473760 CrossRefGoogle Scholar
  19. 19.
    Boggs JM, Rangaraj G, Gao W, Heng YM (2006) Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro. Biochemistry 45(2):391–401.  https://doi.org/10.1021/bi0519194 CrossRefGoogle Scholar
  20. 20.
    Hardy RJ, Lazzarini RA, Colman DR, Friedrich VL Jr. (1996) Cytoplasmic and nuclear localization of myelin basic proteins reveals heterogeneity among oligodendrocytes. J Neurosci Res 46(2):246–257.  https://doi.org/10.1002/(SICI)1097-4547(19961015)46:2%3C246::AID-JNR13%3E3.0.CO;2-0 CrossRefGoogle Scholar
  21. 21.
    Carre JL, Goetz BD, O’Connor LT, Bremer Q, Duncan ID (2002) Mutations in the rat myelin basic protein gene are associated with specific alterations in other myelin gene expression. Neurosci Lett 330(1):17–20CrossRefGoogle Scholar
  22. 22.
    Travers TS, Harlow L, Rosas IO, Gochuico BR, Mikuls TR, Bhattacharya SK, Camacho CJ, Ascherman DP (2016) Extensive citrullination promotes immunogenicity of HSP90 through protein unfolding and exposure of cryptic epitopes. J Immunol (Baltimore, Md: 1950) 197(5):1926–1936.  https://doi.org/10.4049/jimmunol.1600162 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Bascom Palmer Eye InstituteUniversity of MiamiMiamiUSA
  2. 2.Neuroscience Graduate ProgramUniversity of MiamiMiamiUSA
  3. 3.Department of Ophthalmology & Bascom Palmer Eye InstituteUniversity of MiamiMiamiUSA

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