Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells
Yuya Nagasawa1, Yu Takahashi1, Wataru Itani1, Hitoshi Watanabe1, Yusuke Hidaka1, Shotaro Morita1, Kei Suzuki1, Kouichi Watanabe1, Shyuichi Ohwada1, Haruki Kitazawa2, Morikazu Imamura3, Takashi Yokoyama3, Motohiro Horiuchi4, Suehiro Sakaguchi5, Shirou Mohri3, Michael T. Rose6, Tomonori Nochi1, Hisashi Aso1*
1Cellular Biology Laboratory, Tohoku University, Sendai, Japan.
2Food Immunology Group, Tohoku University, Sendai, Japan.
3Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Japan.
4Laboratory of Veterinary Hygiene, Hokkaido University, Sapporo, Japan.
5Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan.
6Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK.
 DOI: 10.4236/ojvm.2015.53007   PDF    HTML   XML   3,740 Downloads   4,735 Views  

Abstract

Microfold (M) cells are a kind of intestinal epithelial cell in the follicle-associated epithelium (FAE) of Peyer’s patches. They can transport antigens and microorganisms to lymphoid tissues. Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder in cattle. It is linked to variant Creutzfeldt-Jakob disease in humans. Although it is thought that M cells transport the BSE agent, the exact mechanism by which it crosses the intestinal barrier is not clear. We have bovine intestinal epithelial cell line (BIE cells), which can differentiate into the M cell type in vitro after stimulation, and which is able to transport the BSE agent. We show here that M cells are able to incorporate large numbers of PrP coated magnetic particles into intracellular vesicles, which we collected. The results of 2-DE show a specific protein associated with the PrP-coated particles, compared with non-coated particles. This protein was identified as aldolase A, a glycolytic pathway enzyme, using LC-MS/MS analysis. Aldolase A was synthesized and secreted by BIE cells, and increased during M cell differentiation. In the villi of the bovine intestine, aldolase A was detected on the surface of the epithelium and in the mucus droplet of goblet cells. In the FAE of bovine jejunal and ileal Peyer’s patches, aldolase A was localized on the surface and the apical part of the M cells. The binding of rbPrP to aldolase A was clearly detected and inhibited by pre-treatment of anti-aldolase A antibody. Aldolase A was co-stained with incorporated PrPSc in M-BIE cells. These results suggest that bovine M cells and goblet cells synthesize aldolase A, and that aldolase A may have the ability to bind PrP and associate with PrP in cellular vesicles. Therefore, aldolase A-positive M cells may play a key role in the invasion of BSE into the body.

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Nagasawa, Y. , Takahashi, Y. , Itani, W. , Watanabe, H. , Hidaka, Y. , Morita, S. , Suzuki, K. , Watanabe, K. , Ohwada, S. , Kitazawa, H. , Imamura, M. , Yokoyama, T. , Horiuchi, M. , Sakaguchi, S. , Mohri, S. , Rose, M. , Nochi, T. and Aso, H. (2015) Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells. Open Journal of Veterinary Medicine, 5, 43-60. doi: 10.4236/ojvm.2015.53007.

Conflicts of Interest

The authors declare no conflicts of interest.

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