Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells

• 作者: Haruki Kitazawa Hisashi Aso Hitoshi Watanabe Kei Suzuki Kouichi Watanabe Michael T. Rose Morikazu Imamura Motohiro Horiuchi Shirou Mohri Shotaro Morita Shyuichi Ohwada Suehiro Sakaguchi Takashi Yokoyama Tomonori Nochi Wataru Itani Yu Takahashi Yusuke Hidaka Yuya Nagasawa
• 来源期刊: 兽医学(英文)
• 学科: 医学
• 关键词: Peyer’s PATCH M Cell BIE Cells ALDOLASE A PRP Binding Protein
• 年，卷（期）: 2015,（3）
• 页码范围: 43-60
• 页数: 18页
• 分类号: R73

摘要

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.