{"created":"2021-03-01T06:20:00.623594+00:00","id":3371,"links":{},"metadata":{"_buckets":{"deposit":"288fd0bc-fb3c-495a-9813-771a76dba8a9"},"_deposit":{"id":"3371","owners":[],"pid":{"revision_id":0,"type":"depid","value":"3371"},"status":"published"},"_oai":{"id":"oai:repository.dl.itc.u-tokyo.ac.jp:00003371"},"item_7_alternative_title_1":{"attribute_name":"\u305d\u306e\u4ed6\u306e\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_alternative_title":"\u30ed\u30c9\u30d7\u30b7\u30f3\u578bGPCR\u306e\u819c\u8cab\u901a\u9818\u57df\u306b\u4fdd\u5b58\u3055\u308c\u305f\u30a2\u30df\u30ce\u9178\u6b8b\u57fa\u306e\u54c1\u8cea\u7ba1\u7406\u304a\u3088\u3073\u6a5f\u80fd\u306b\u304a\u3051\u308b\u91cd\u8981\u6027\u306b\u95a2\u3059\u308b\u7814\u7a76"}]},"item_7_biblio_info_7":{"attribute_name":"\u66f8\u8a8c\u60c5\u5831","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-03-23","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{}]}]},"item_7_date_granted_25":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u5e74\u6708\u65e5","attribute_value_mlt":[{"subitem_dategranted":"2009-03-23"}]},"item_7_degree_grantor_23":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u6a5f\u95a2","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"University of Tokyo (\u6771\u4eac\u5927\u5b66)"}]}]},"item_7_degree_name_20":{"attribute_name":"\u5b66\u4f4d\u540d","attribute_value_mlt":[{"subitem_degreename":"\u535a\u58eb(\u533b\u5b66)"}]},"item_7_description_5":{"attribute_name":"\u6284\u9332","attribute_value_mlt":[{"subitem_description":"Several amino acid residues in the transmembrane (TM) domains of rhodopsin-type G-protein coupled receptors (GPCRs) are conserved. Here, I showthat mutations in several of these residues interfere the export of GPCRs by the endoplasmic reticulum (ER), and ligands specific for these receptors have the potential to rescue the ER retention. In HeLa cells, replacement of several conserved residues in TM2, TM6, and TM7 by alanine resulted in a significant reduction of cell surface expression of the platelet-activating factor receptor (PAFR). In particular, the importance of the aspartic acid in TM2 and the proline in TM6 were confirmed in two other GPCRs, leukotriene B4 type-2 receptor and GPR43. Although PAFRs containing these mutated residues, including D63A and P247A, accumulated in the ER, the cell surface expression of these receptors was facilitated by the addition of the PAFR ligands methylcarbamyl PAF or Y-24180. Because the Y-24180 treatment reduced the ubiquitination of the mutant PAFRs and increased the proportion of fully glycosylated forms, the augmentation of the cell surface receptor is due to the facilitation of ER export. While the surface-trafficked P247A mutant showed the potential to elicit an increase of intracellular Ca2+ by PAF, D63A mutants lacked this signaling ability. Taken together, my data indicate that deficiency of conserved amino acid residues in GPCRs inhibits their export from the ER, and that treatmentwith pharmacological chaperones allows them to pass the quality control system in the ER, even though some of them are dysfunctional receptors","subitem_description_type":"Abstract"}]},"item_7_dissertation_number_26":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u756a\u53f7","attribute_value_mlt":[{"subitem_dissertationnumber":"\u7532\u7b2c24859\u53f7"}]},"item_7_full_name_3":{"attribute_name":"\u8457\u8005\u5225\u540d","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"8121","nameIdentifierScheme":"WEKO"}],"names":[{"name":"\u30d2\u30ed\u30bf, \u30ce\u30d6\u30a2\u30ad"}]}]},"item_7_identifier_registration":{"attribute_name":"ID\u767b\u9332","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15083/00003365","subitem_identifier_reg_type":"JaLC"}]},"item_7_select_21":{"attribute_name":"\u5b66\u4f4d","attribute_value_mlt":[{"subitem_select_item":"doctoral"}]},"item_7_text_22":{"attribute_name":"\u5b66\u4f4d\u5206\u91ce","attribute_value_mlt":[{"subitem_text_value":"Medical Science (\u533b\u5b66)"}]},"item_7_text_24":{"attribute_name":"\u7814\u7a76\u79d1\u30fb\u5c02\u653b","attribute_value_mlt":[{"subitem_text_value":"Department of Internal Medicine, Graduate School of Medicine (\u533b\u5b66\u7cfb\u7814\u7a76\u79d1\u5185\u79d1\u5b66\u5c02\u653b)"}]},"item_7_text_27":{"attribute_name":"\u5b66\u4f4d\u8a18\u756a\u53f7","attribute_value_mlt":[{"subitem_text_value":"\u535a\u533b\u7b2c3279\u53f7"}]},"item_7_text_4":{"attribute_name":"\u8457\u8005\u6240\u5c5e","attribute_value_mlt":[{"subitem_text_value":"\u6771\u4eac\u5927\u5b66\u5927\u5b66\u9662\u533b\u5b66\u7cfb\u7814\u7a76\u79d1\u5185\u79d1\u5b66\u5c02\u653b"}]},"item_creator":{"attribute_name":"\u8457\u8005","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"\u5ee3\u7530, \u4fe1\u54f2"}],"nameIdentifiers":[{"nameIdentifier":"8120","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"\u30d5\u30a1\u30a4\u30eb\u60c5\u5831","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-05-31"}],"displaytype":"detail","filename":"41_hirota.pdf","filesize":[{"value":"29.0 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"41_hirota.pdf","url":"https://repository.dl.itc.u-tokyo.ac.jp/record/3371/files/41_hirota.pdf"},"version_id":"b2342586-8b21-4d95-99b3-9dffffe5b36e"}]},"item_language":{"attribute_name":"\u8a00\u8a9e","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"\u8cc7\u6e90\u30bf\u30a4\u30d7","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Importance of conserved amino acids in transmembrane domains of rhodopsin type GPCRs in their quality control and function","item_titles":{"attribute_name":"\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_title":"Importance of conserved amino acids in transmembrane domains of rhodopsin type GPCRs in their quality control and function"}]},"item_type_id":"7","owner":"1","path":["9/233/280","125/355/356"],"pubdate":{"attribute_name":"\u516c\u958b\u65e5","attribute_value":"2012-04-05"},"publish_date":"2012-04-05","publish_status":"0","recid":"3371","relation_version_is_last":true,"title":["Importance of conserved amino acids in transmembrane domains of rhodopsin type GPCRs in their quality control and function"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2021-03-01T19:46:34.270107+00:00"}