Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-28838
Bremer, J; Baumann, F; Tiberi, C; Wessig, C; Fischer, H; Schwarz, P; Steele, A D; Toyka, K V; Nave, K A; Weis, J; Aguzzi, A (2010). Axonal prion protein is required for peripheral myelin maintenance. Nature Neuroscience, 13(3):310-318.
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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:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||20 Mar 2010 12:10|
|Last Modified:||19 Apr 2014 01:37|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 103|
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