A Caltech Library Service

Axonal prion protein is required for peripheral myelin maintenance

Bremer, Juliane and Baumann, Frank and Tiberi, Cinzia and Wessig, Carsten and Fischer, Heike and Schwarz, Petra and Steele, Andrew D. and Toyka, Klaus V. and Nave, Klaus-Armin and Weis, Joachim and Aguzzi, Adriano (2010) Axonal prion protein is required for peripheral myelin maintenance. Nature Neuroscience, 13 (3). pp. 310-318. ISSN 1097-6256.

[img] PDF - Published Version
Restricted to Repository administrators only
See Usage Policy.

[img] PDF (Supplementary Figures 1–15 and Supplementary Table 1) - Supplemental Material
Restricted to Repository administrators only
See Usage Policy.


Use this Persistent URL to link to this item:


The integrity of peripheral nerves relies on communication between axons and Schwann cells. The axonal signals that ensure myelin maintenance are distinct from those that direct myelination and are largely unknown. Here we show that ablation of the prion protein PrP^C triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains. Ablation of the neighboring Prnd locus, or inbreeding to four distinct mouse strains, did not modulate the CDP. CDP was triggered by depletion of PrP^C specifically in neurons, but not in Schwann cells, and was suppressed by PrP^C expression restricted to neurons but not to Schwann cells. CDP was prevented by PrP^C variants that undergo proteolytic amino-proximal cleavage, but not by variants that are nonpermissive for cleavage, including secreted PrP^C lacking its glycolipid membrane anchor. These results indicate that neuronal expression and regulated proteolysis of PrP^C are essential for myelin maintenance.

Item Type:Article
Related URLs:
Additional Information:© 2010 Nature Publishing Group. Received 09 November 2009. Accepted 16 December 2009. Published online 24 January 2010. We thank M. Delic, R. Moos, D. Goriounov, C. Tostado, H. Mader, K. Nairz, M. Bieri, N. Wey and D. Meijer for methodological advice and technical help. G. Mallucci provided tgNFH-Cre and tgPrnploxP mice, D. Meijer provided tgDhh-Cre mice, J.C. Manson provided PrnpEdbg/Edbg mice, J. Collinge provided Prnpo/o FVB mice, S. Lindquist and W. Jackson provided PrnpGFP/GFP mice and P. Saftig and A. Rittger provided nerves from BACE1−/− mice. We thank W.B. Macklin for the PLP plasmid; T. Rülicke for pronuclear injections and H. Welzl, I. Drescher and S. Wirth for help with behavioral tests. J.A. Girault and M.T. Dours-Zimmermann donated anti-paranodine/Caspr and anti-versican antibodies, respectively. We thank B. Seifert for statistical consulting. A.A. received an ERC Advanced Investigator Grant and grants from the European Union (PRIORITY and LUPAS), the Novartis Foundation and the Swiss National Foundation. J.B. received a Career Development award from the University of Zürich. C.W. and K.V.T. were supported by the Departmental Research Fund. Author Contributions: J.B. and A.A. designed the study and wrote the manuscript. J.B., F.B., C.T., C.W., H.F., P.S., A.D.S., K.V.T. and J.W. did the experiments. J.B., F.B., C.T., C.W., H.F., A.D.S., K.V.T., K.-A.N., J.W. and A.A. analyzed the data.
Funding AgencyGrant Number
Novartis FoundationUNSPECIFIED
Swiss National FoundationUNSPECIFIED
University of ZurichUNSPECIFIED
Departmental Research FundUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20100316-110157249
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17755
Deposited By: Tony Diaz
Deposited On:05 Apr 2010 15:32
Last Modified:03 Oct 2019 01:32

Repository Staff Only: item control page