%0 Journal Article
%T Identification and structural analysis of C-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases
%A Fumiko Shinkai-Ouchi
%A Yoshio Yamakawa
%A Hideyuki Hara
%A Minoru Tobiume
%A Masahiro Nishijima
%A Kentaro Hanada
%A Ken'ichi Hagiwara
%J Proteome Science
%D 2010
%I BioMed Central
%R 10.1186/1477-5956-8-53
%X In a proteomic analysis of soluble proteins in the brains of mice challenged intracerebrally with scrapie prion (Obihiro I strain), we found that the amount of the full-length form of collapsin response mediator protein-2 (CRMP-2; 61 kDa) decreased in the late stages of the disease, while the amount of its truncated form (56 kDa) increased to comparable levels observed for the full-length form. Detailed analysis by liquid chromatography-electrospray ionization-tandem mass spectrometry showed that the 56-kDa form (named CRMP-2-ĶĪC) lacked the sequence from serine518 to the C-terminus, including the C-terminal phosphorylation sites important for the regulation of axonal growth and axon-dendrite specification in developing neurons. The invariable size of the mRNA transcript in Northern blot analysis suggested that the truncation was due to post-translational proteolysis. By overexpression of CRMP-2-ĶĪC in primary cultured neurons, we observed the augmentation of the development of neurite branch tips to the same levels as for CRMP-2T514A/T555A, a non-phosphorylated mimic of the full-length protein. This suggests that the increased level of CRMP-2-ĶĪC in the brain modulates the integrity of neurons, and may be involved in the pathogenesis of the neuronal abnormalities observed in the late stages of the disease.We identified the presence of CRMP-2-ĶĪC in the brain of a murine model of prion disease. Of note, C-terminal truncations of CRMP-2 have been recently observed in models for neurodegenerative disorders such as ischemia, traumatic brain injury, and Wallerian degeneration. While the structural identity of CRMP-2-ĶĪC in those models remains unknown, the present study should provide clues to the molecular pathology of degenerating neurons in prion diseases in connection with other neurodegenerative disorders.Transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease, Gerstmann-StrĢŋussler-Schein
%U http://www.proteomesci.com/content/8/1/53