Enhanced detection and retrograde axonal transport of PrPc in peripheral nerve.
Neuroinvasion of the CNS during orally acquired transmissible spongiform encephalopathies (TSEs) may involve the transport of the infectious agent from the periphery to the CNS via the peripheral nerves. If this occurs within axons, the mechanism of axonal transport may be fundamental to the process. In studies of peripheral nerve we observed that the cellular prion protein (PrPc) is highly resistant to detergent extraction. The implication of this is an underestimation of the abundance of PrPc in peripheral nerve. We have developed nerve extraction conditions that enhance the quantification of the protein in nerve 16-fold. Application of these conditions to evaluate the accumulation of PrPc distal to a cut nerve now reveals that PrPc is retrogradely transported from the axon ending. These results provide a potential cellular mechanism for TSE infectivity to gain entry to the CNS from the periphery.
Moya
Kenneth L
KL
Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique Unité de Recherche Associée (CEA-CNRS URA), Service Hospitalier Frédéric Joliot, Orsay, France. moya@shfj.cea.fr
Hässig
Raymonde
R
Créminon
Christophe
C
Laffont
Isabelle
I
Di Giamberardino
Luigi
L
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D007158:Immunologic Techniques; D010525:Peripheral Nerves / Q000737:chemistry* / Q000378:metabolism*; D018621:PrPC Proteins / Q000032:analysis* / Q000378:metabolism*; D015203:Reproducibility of Results; D012584:Sciatic Nerve / Q000737:chemistry / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
D018621:PrPC Proteins; D012967:Sodium Dodecyl Sulfate