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Author Notes:

Corresponding author. Email: melanie.ohi@vanderbilt.edu (M.D.O.); chuck.sanders@vanderbilt.edu (C.R.S.)

See publication for full list of author contributions.

We acknowledge cryo-EM facilities management support from Collier.

We also thank members of the Ohi Lab—L. Lapointe, B. Carter, and T. Iverson—for critical reading of the manuscript.

We thank the Vanderbilt Center for Structural Biology for support of the Structural Electron Microscopy Facility.

The authors declare that they have no competing interests.

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

Additional data related to this paper may be requested from the authors.


Research Funding:

This work was supported by grants R01 NS058815, R01 NS095989 (to C.R.S. and M.D.O.), R01 NS066927 (to C.R.S.), R01GM104540 (to E.R.W.), R01GM1145661 (E.R.W), and NSF-0923395 (to E.R.W.), as well as grants from the Emory University, the Children’s Healthcare of Atlanta, the Georgia Research Alliance, the Center for AIDS Research at Emory University (P30 AI050409), and the James B. Pendleton Charitable Trust (to E.R.W.).

K.F.M. was supported by NIH T32 GM08320 and NSF Predoctoral Fellowship DGE090966. J.P.S. was supported by NIH F32 GM110929. J.T.M. was supported by T32 GM008320.


  • Charcot-Marie-Tooth Disease
  • Electron Microscopy
  • Membrane
  • Myelin
  • Neuropathy
  • PNS
  • Peripheral Myelin Protein 22
  • Peripheral Nervous System
  • Reconstitution

Peripheral myelin protein 22 alters membrane architecture.

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Journal Title:

Science Advances


Volume 3, Number 7


, Pages e1700220-e1700220

Type of Work:

Article | Final Publisher PDF


Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin.

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© 2017 The Authors, some rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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