University of Oulu

Raasakka A, Linxweiler H, Brophy PJ, Sherman DL and Kursula P (2019) Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F. Front. Mol. Neurosci. 12:84. doi: 10.3389/fnmol.2019.00084

Direct binding of the flexible C-terminal segment of periaxin to β4 integrin suggests a molecular basis for CMT4F

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Author: Raasakka, Arne1; Linxweiler, Helen1; Brophy, Peter J.2;
Organizations: 1Department of Biomedicine, University of Bergen, Bergen, Norway
2Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
3Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.2 MB)
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Language: English
Published: Frontiers Media, 2019
Publish Date: 2019-10-21


The process of myelination in the nervous system requires a coordinated formation of both transient and stable supramolecular complexes. Myelin-specific proteins play key roles in these assemblies, which may link membranes to each other or connect the myelinating cell cytoskeleton to the extracellular matrix. The myelin protein periaxin is known to play an important role in linking the Schwann cell cytoskeleton to the basal lamina through membrane receptors, such as the dystroglycan complex. Mutations that truncate periaxin from the C terminus cause demyelinating peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease type 4F, indicating a function for the periaxin C-terminal region in myelination. We identified the cytoplasmic domain of β4 integrin as a specific high-affinity binding partner for periaxin. The C-terminal region of periaxin remains unfolded and flexible when bound to the third fibronectin type III domain of β4 integrin. Our data suggest that periaxin is able to link the Schwann cell cytoplasm to the basal lamina through a two-pronged interaction via different membrane protein complexes, which bind close to the N and C terminus of this elongated, flexible molecule.

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Series: Frontiers in molecular neuroscience
ISSN: 1662-5099
ISSN-E: 1662-5099
ISSN-L: 1662-5099
Volume: 12
Article number: 84
DOI: 10.3389/fnmol.2019.00084
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Funding: This work was financially supported by the Norwegian Research Council (Norges Forskningsråd) travel grant to PK (SYNKNØYT 247669), as well as a Wellcome Trust (107008/Z/15/Z) grant to PB.
Copyright information: © 2019 Raasakka, Linxweiler, Brophy, Sherman and Kursula. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.