Inherited demyelinating peripheral neuropathies: relating myelin packing abnormalities to P0 molecular defects

Journal of Neuroscience Research
Daniel A KirschnerP A Bolhuis

Abstract

P0-glycoprotein, the major integral membrane protein of peripheral nerve myelin, is thought to mediate myelination and membrane interactions via its extracellular domain (P0-ED). Molecular modeling of P0-ED has suggested which of its amino acid side-chains may be involved in heterophilic and homophilic adhesions. We previously showed that some of these amino acids are the same ones that are substituted or deleted due to mutations in the human gene for P0 (MPZ), which correlate with certain cases of demyelinating motor and sensory peripheral neuropathies. In the current study, high magnification electron microscopy was used to examine the myelin membrane packing in sural nerve biopsies from patients with MPZ mutations. We found that there were distinguishable ultrastructural phenotypes that could be explained by the alterations in P0-ED. These phenotypes, which were not observed in a control nerve, included widening or irregularity of the extracellular apposition alone (delta Ser34; Arg69Cys), widening at both the extracellular and cytoplasmic appositions (Arg69His), the presence of focal bridges in the widened extracellular space (Arg69His), and a diminished (Arg69Cys) or absence (Arg69His) of staining of the double intraperiod...Continue Reading

References

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Citations

Jul 17, 1999·Journal of Neurology, Neurosurgery, and Psychiatry·F L MastagliaN G Laing
Oct 13, 2010·The Journal of Biological Chemistry·Robin L AvilaDaniel A Kirschner
Jun 13, 2012·Brain : a Journal of Neurology·Mario A C SaportaMichael E Shy
Aug 28, 2015·Brain : a Journal of Neurology·Oranee SanmaneechaiUNKNOWN Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC)
Nov 27, 2019·Cell Biology International·Fatemeh GhanavatinejadMohammad-Saeid Jami
Nov 22, 2000·The Journal of Cell Biology·S C PrevitaliM L Feltri
Dec 3, 1999·Journal of the Neurological Sciences·A OhnishiM Ikeda
Apr 18, 2018·Molecular and Cellular Biology·Wang-Yang XuZhu-Gang Wang
Aug 19, 2007·Biophysical Journal·XiaoYang LuoDaniel A Kirschner

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