The cytoplasmic tail of myelin protein zero induces morphological changes in lipid membranes
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Abstract
The major myelin protein expressed by the peripheral nervous system Schwann cells is protein zero (P0), which represents 50% of the total protein content in myelin. This 30-kDa integral membrane protein consists of an immunoglobulin (Ig)-like domain, a transmembrane helix, and a 69-residue C-terminal cytoplasmic tail (P0ct). The basic residues in P0ct contribute to the tight packing of myelin lipid bilayers, and alterations in the tail affect how P0 functions as an adhesion molecule necessary for the stability of compact myelin. Several neurodegenerative neuropathies are related to P0, including the more common Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS) as well as rare cases of motor and sensory polyneuropathy. We found that high P0ct concentrations affected the membrane properties of bicelles and induced a lamellar-to-inverted hexagonal phase transition, which caused bicelles to fuse into long, protein-containing filament-like structures. These structures likely reflect the formation of semicrystalline lipid domains with potential relevance for myelination. Not only is P0ct important for stacking lipid membranes, but time-lapse fluorescence microscopy also shows that it might affect membrane properties during myelination. We further describe recombinant production and low-resolution structural characterization of full-length human P0. Our findings shed light on P0ct effects on membrane properties, and with the successful purification of full-length P0, we have new tools to study the role of P0 in myelin formation and maintenance in vitro.
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Myelination, Dysmyelination, and Demyelination
Harry, G. J., & Toews, A. D. (1998) · Elsevier eBooks · doi:10.1016/b978-012648860-9.50007-8 · Cited by 27 · see citing works
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Crystal structure of the extracellular domain of human myelin protein zero
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Liposomes on a Streptavidin Crystal: A System to Study Membrane Proteins by Cryo-EM
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Mechanisms of membrane protein crystallization in ‘bicelles’
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Characterization of the Effect on Adhesion of Different Mutations in Myelin P0 Protein
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Increased Conduction Velocity as a Result of Myelination
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Shaharabani, R., Ram-On, M., Talmon, Y., & Beck, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804275115 · Cited by 23 · see citing works
Annexins A1 and A2 Accumulate and Are Immobilized at Cross-Linked Membrane–Membrane Interfaces
Klenow, M. B., Iversen, C., Lund, F. W., Mularski, A., Heitmann, A. S. B., Dias, C., Nylandsted, J., & Simonsen, A. C. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00126 · Cited by 23 · see citing works
Self-citationGain of glycosylation: A new pathomechanism of myelin protein zero mutations
Prada, V., Passalacqua, M., Bono, M., Luzzi, P., Scazzola, S., Nobbio, L., Capponi, S., Bellone, E., Mandich, P., Mancardi, G., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22695 · Cited by 23 · see citing works
Confirmation of proximal 1q duplication using fluorescence in situ hybridization
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Measurement of the coherent beam properties at the CoSAXS beamline
Kahnt, M., Klementiev, K., Haghighat, V., Weninger, C., Plivelic, T. S., Terry, A. E., & Björling, A. (2021) · Journal of Synchrotron Radiation · doi:10.1107/s1600577521009140 · Cited by 23 · see citing works
Laulumaa, S., Nieminen, T., Raasakka, A., Krokengen, O. C., Safaryan, A., Hallin, E. I., Brysbaert, G., Lensink, M. F., Ruskamo, S., Vattulainen, I., et al. (2018) · BMC Structural Biology · doi:10.1186/s12900-018-0087-2 · Cited by 22 · see citing works
Self-citationP0 (Protein Zero) Mutation S34C Underlies Instability of Internodal Myelin in S63C Mice
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Self-citationRaasakka, A., Jones, N. C., Hoffmann, S. V., & Kursula, P. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.025 · Cited by 19 · see citing works
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Identification and in silico analysis of 14 novel GJB1, MPZ and PMP22 gene mutations
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Self-citationExpanding the Toolbox for Bicelle-Forming Surfactant–Lipid Mixtures
Giudice, R. D., Paracini, N., Laursen, T., Blanchet, C. E., Roosen‐Runge, F., & Cárdenas, M. (2022) · Molecules · doi:10.3390/molecules27217628 · Cited by 12 · see citing works
Changes in the anisotropy of oriented membrane dynamics induced by myelin basic protein
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Self-citationMy first electron density map: A beginner's guide to small angle X-ray diffraction
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Intrinsic dynamical fluctuations of PNS myelinPreprint
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Interactions between DMPC Model Membranes, the Drug Naproxen, and the Saponin β-Aescin
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1 of the 129 references couldn’t be matched to a known paper.
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Lipid metabolism alterations in peripheral neuropathies
Silva, A., Prior, R. C., D’Antonio, M., Swinnen, J. V., & Bosch, L. V. D. (2025) · Neuron · doi:10.1016/j.neuron.2025.04.006 · Cited by 33 · see citing works
Hoffmann, S. V., Jones, N. C., & Rodger, A. (2025) · QRB Discovery · doi:10.1017/qrd.2025.4 · Cited by 15 · see citing works
Krokengen, O. C., Raasakka, A., Klenow, M. B., Pal, A., Hetland, Ø., Mularski, A., Ruskamo, S., Pedersen, J. S., Simonsen, A. C., & Kursula, P. (2025) · FEBS Journal · doi:10.1111/febs.70111 · Cited by 3 · see citing works
Self-citationMicroalgae-derived vesicles as potential carriers for therapeutic biomacromolecules
Klacsová, M., Sebök‐Nagy, K., Páli, T., Chovancová, M., Almásy, L., & Uhrı́ková, D. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.107985 · Cited by 2 · see citing works
Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?
Kuipers, K., Vanherle, S., Poelmans, K., Wolfs, E., Bogie, J. F. J., & Vangansewinkel, T. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00932-6 · Cited by 1 · see citing works
Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease
Sanders, C. R., Carter, B. D., Wilkinson, M. C., Li, G., & Stefanski, K. M. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.6c00096 · Cited by 1 · see citing works
- Authors
- Krokengen, O. C., Touma, C., Mularski, A., Sutinen, A., Dunkel, R., Ytterdal, M., Raasakka, A., Mertens, H. D. T., Simonsen, A. C., & Kursula, P.
- Affiliations
- University of Bergen (NO)
- University of Oulu (FI)
- University of Southern Denmark (DK)
- Deutsches Elektronen-Synchrotron DESY (DE)
- Corresponding author
- Kursula, Petri
- ORCID
- Venue
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Publisher
- Elsevier BV
- Published
- 2024-10
- Volume
- 1866
- Issue
- 7
- Pages
- 184368
- ISSN
- 0005-2736 (ISSN-L)
- OpenAlex
- W4400315566
- Cited by
- 7
- References
- 129
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by)
- Funders
- Diamond Light Source
- European Commission (EU-H2020, 101004806, HORIZON2020, H2020)
- VINNOVA (2019‐02496, 2018-07152, 2018-04969)
- Svenska Forskningsrådet Formas (2018-07152, 2019-02496)
- Vetenskapsrådet (2018–04969, 07152, 2019–02496, 201807152, 2018-)
- Universitetet i Bergen
- Norges Forskningsråd (245922, 245828, 324877)
- Horizon 2020 Framework Programme (EU‐H2020, 101004806, 2018-07152)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- myelin protein zero, Schwann cells, myelin, bicelles, membrane fusion, myelination, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, peripheral neuropathy
- MeSH terms
- Cytoplasm, Humans, Lipid Bilayers, Membrane Lipids, Myelin Sheath, Myelin P0 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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