Axonal prion protein is required for peripheral myelin maintenance

Nat Neurosci. 2010 Mar;13(3):310-8. doi: 10.1038/nn.2483. Epub 2010 Jan 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Chronic Disease
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • GPI-Linked Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Myelin Sheath / physiology*
  • Myelin Sheath / ultrastructure
  • Nerve Fibers, Myelinated / physiology*
  • Nerve Fibers, Myelinated / ultrastructure
  • Neurons / physiology
  • Neurons / ultrastructure
  • Peripheral Nerves / physiology*
  • Peripheral Nerves / ultrastructure
  • Polyneuropathies / metabolism
  • Polyneuropathies / pathology
  • PrPC Proteins / genetics
  • PrPC Proteins / metabolism*
  • Prions / genetics
  • Prions / metabolism
  • Schwann Cells / physiology
  • Schwann Cells / ultrastructure
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology


  • GPI-Linked Proteins
  • PrPC Proteins
  • Prions
  • Prnd protein, mouse