{"id":670,"date":"2017-03-14T11:53:36","date_gmt":"2017-03-14T02:53:36","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2011year\/yamamoto-masahiro-takeda-kiyoshi"},"modified":"2017-04-28T16:08:06","modified_gmt":"2017-04-28T07:08:06","slug":"article03","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2011year\/article03","title":{"rendered":"YAMAMOTO Masahiro, TAKEDA Kiyoshi \u226aImmune Regulation\u226b <span>\u201cATF6\u03b2 is a host cellular target of the Toxoplasma gondii virulence factor ROP18\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2011year\/article03\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1> \u5c71\u672c \u96c5\u88d5\u3001\u7af9\u7530 \u6f54 \u226a\u514d\u75ab\u5236\u5fa1\u5b66\u226b<\/h1>\n\n --><\/p>\n<p class=\"figure\"><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/yamamoto20110613-1.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/yamamoto20110613-1.jpeg\" alt=\"\u514d\u75ab\u5236\u5fa1\u5b66-1\" height=\"133\" width=\"200\" \/><br \/><span>Click to enlarge<\/span> <\/a><\/p>\n<p>  <a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/yamamoto20110613-2.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/yamamoto20110613-2.jpeg\" alt=\"\u514d\u75ab\u5236\u5fa1\u5b66-2\" height=\"191\" width=\"149\" \/><br \/><span class=\"click\">Click to enlarge<\/span> <\/a>\n  <\/p>\n<p>2011-6-13<br \/>\n  <span class=\"lineFrame\">Publish<\/span>The Journal of Experimental Medicine&nbsp; 208:1533-1546 (2011)<\/p>\n<p><!-- \n\n<h3><strong>\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u767a\u75c5\u306e\u6c7a\u5b9a\u7684\u75c5\u539f\u6027\u56e0\u5b50ROP18\u306e\u4f5c\u7528\u6a5f\u5e8f\u306e\u89e3\u660e<\/strong><\/h3>\n\n\n\n\n<p> \u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u306f\u30a8\u30a4\u30ba\u60a3\u8005\u3084\u6297\u304c\u3093\u5264\u3092\u591a\u7528\u3059\u308b\u764c\u60a3\u8005\u306a\u3069\u514d\u75ab\u6291\u5236\u72b6\u614b\u306b\u3042\u308b\u4eba\u9593\u3084\u52d5\u7269\u3067\u8133\u75c7\u304c\u304a\u3053\u308a\u3001\u91cd\u7be4\u306a\u795e\u7d4c\u75c7\u72b6\u3092\u5f15\u304d\u8d77\u3053\u3059\u5927\u5909\u6b7b\u4ea1\u7387\u306e\u9ad8\u3044\u4eba\u755c\u5171\u901a\u5bc4\u751f\u866b\u75c5\u3067\u3059\u3002\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u3092\u5f15\u304d\u8d77\u3053\u3059\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u539f\u866b\u306f\u3001\u4e16\u754c\u4eba\u53e3\u306e\u7d043\u5206\u306e1\u304c\u611f\u67d3\u3057\u3066\u3044\u308b\u3068\u3055\u308c\u3001\u5065\u5e38\u4eba\u3067\u306f\u3055\u307b\u3069\u554f\u984c\u306a\u3044\u3082\u306e\u306e\u598a\u5a66\u304c\u521d\u3081\u3066\u611f\u67d3\u3057\u305f\u969b\u306b\u306f\u80ce\u5150\u306e\u6d41\u7523\u3084\u65b0\u751f\u5150\u306e\u5148\u5929\u6027\u6c34\u982d\u75c7\u3092\u5f15\u304d\u8d77\u3053\u3059\u3053\u3068\u3082\u3042\u308b\u3001\u4e88\u5f8c\u304c\u5927\u5909\u60aa\u3044\u91cd\u8981\u75c5\u539f\u4f53\u3067\u3059\u3002\u5bc4\u751f\u866b\u304c\u611f\u67d3\u3059\u308b\u3068\u4eba\u9593\u3084\u52d5\u7269\u306a\u3069\u306e\u5bbf\u4e3b\u3067\u306f\u514d\u75ab\u30b7\u30b9\u30c6\u30e0\u306b\u3088\u308b\u6392\u9664\u6a5f\u69cb\u304c\u4f5c\u52d5\u3057\u307e\u3059\u304c\u3001\u75c5\u539f\u6027\u306e\u9ad8\u3044\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u539f\u866b\u611f\u67d3\u3067\u306f\u5bbf\u4e3b\u514d\u75ab\u7cfb\u304c\u6291\u5236\u3055\u308c\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u304c\u767a\u75c7\u3059\u308b\u3053\u3068\u304c\u8fd1\u5e74\u308f\u304b\u3063\u3066\u304d\u307e\u3057\u305f\u3002\u3057\u304b\u3057\u3001\u305d\u306e\u9ad8\u75c5\u539f\u6027\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u539f\u866b\u306b\u3088\u308b\u5bbf\u4e3b\u514d\u75ab\u6291\u5236\u6a5f\u69cb\u306e\u5177\u4f53\u7684\u306a\u30e1\u30ab\u30cb\u30ba\u30e0\u306f\u4e0d\u660e\u306e\u307e\u307e\u3067\u3057\u305f\u3002<br \/>\n  \u4eca\u56de\u672c\u7814\u7a76\u30b0\u30eb\u30fc\u30d7\u306f\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u306e\u30de\u30a6\u30b9\u5b9f\u9a13\u30e2\u30c7\u30eb\u3092\u7528\u3044\u308b\u3053\u3068\u306b\u3088\u308a\u3001\u9ad8\u75c5\u539f\u6027\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u539f\u866b\u304c\u5206\u6ccc\u3059\u308b\u75c5\u539f\u6027\u56e0\u5b50ROP18\u304c\u6025\u6027\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u767a\u75c5\u306e\u969b\u306e\u514d\u75ab\u6291\u5236\u53cd\u5fdc\u306b\u91cd\u8981\u3067\u3042\u308b\u3053\u3068\u3092\u767a\u898b\u3057\u307e\u3057\u305f\u3002\u305d\u306e\u30e1\u30ab\u30cb\u30ba\u30e0\u3068\u3057\u3066\u3001ROP18\u304c\u5bbf\u4e3b\u611f\u67d3\u7d30\u80de\u306b\u6253\u3061\u8fbc\u307e\u308c\u3001\u5bbf\u4e3b\u306e\u30b9\u30c8\u30ec\u30b9\u30bb\u30f3\u30b5\u30fc\u306e\u4e00\u3064\u3067\u3042\u308bATF6\u03b2\u3092\u5206\u89e3\u3057\u6a5f\u80fd\u4e0d\u5168\u306b\u9665\u308c\u308b\u3053\u3068\u3067\u3001\u5bc4\u751f\u866b\u6392\u9664\u306b\u5fc5\u8981\u306a\u2160\u578b\u514d\u75ab\u5fdc\u7b54\u3092\u6291\u5236\u3059\u308b\u3053\u3068\u3092\u898b\u51fa\u3057\u307e\u3057\u305f\u3002\u3053\u306e\u767a\u898b\u306f\u3001ROP1\uff18\u306e\u6a5f\u80fd\u3092\u4eba\u70ba\u7684\u306b\u64cd\u4f5c\u3059\u308b\u3053\u3068\u3067\u3001\u30c8\u30ad\u30bd\u30d7\u30e9\u30ba\u30de\u75c7\u306b\u5bfe\u3059\u308b\u65b0\u305f\u306a\u6cbb\u7642\u6cd5\u306e\u958b\u767a\u306b\u7e4b\u304c\u308b\u6210\u679c\u3068\u3057\u3066\u671f\u5f85\u3055\u308c\u3001\u7c73\u56fd\u533b\u5b66\u96d1\u8a8cJournal of Experimental Medicine\u8a8c\u306b\u63b2\u8f09\u3055\u308c\u307e\u3057\u305f\u3002\u307e\u305f\u3001\u672c\u7814\u7a76\u8ad6\u6587\u306e\u5185\u5bb9\u304c\u63b2\u8f09\u7d19\u306e\u8868\u7d19\u30ab\u30d0\u30fc\u306b\u9078\u3070\u308c\u307e\u3057\u305f\u3002<\/p>\n\n --><\/p>\n<p> The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood.<br \/>\n  In this study, we show that ROP18 targets the host endoplasmic reticulum&ndash;bound transcription factor ATF6\u03b2. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6\u03b2-dependent pathogenicity by interacting with ATF6\u03b2 and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6\u03b2 and for parasite virulence. Consistent with a key role for ATF6\u03b2 in resistance against this intracellular pathogen, ATF6\u03b2-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites.<br \/>\n  The results reveal that interference with ATF6\u03b2-dependent immune responses is a novel pathogenic mechanism induced by ROP18. <\/p>\n<p><span class=\"lineFrame\">URL<\/span><\n<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Click to enlarge Click to enlarge 2011-6-13 PublishThe Journal of Experimental Medicine&nbsp; [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1793,"parent":460,"menu_order":171,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/670"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=670"}],"version-history":[{"count":8,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/670\/revisions"}],"predecessor-version":[{"id":2388,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/670\/revisions\/2388"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/460"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1793"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=670"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}