{"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","sets":["125:355:356","9:233:280"]},"item_7_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"ロドプシン型GPCRの膜貫通領域に保存されたアミノ酸残基の品質管理および機能における重要性に関する研究"}]},"item_7_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-03-23","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{}]}]},"item_7_date_granted_25":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2009-03-23"}]},"item_7_degree_grantor_23":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"University of Tokyo (東京大学)"}]}]},"item_7_degree_name_20":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_5":{"attribute_name":"抄録","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":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第24859号"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"8121","nameIdentifierScheme":"WEKO"}],"names":[{"name":"ヒロタ, ノブアキ"}]}]},"item_7_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15083/00003365","subitem_identifier_reg_type":"JaLC"}]},"item_7_select_21":{"attribute_name":"学位","attribute_value_mlt":[{"subitem_select_item":"doctoral"}]},"item_7_text_22":{"attribute_name":"学位分野","attribute_value_mlt":[{"subitem_text_value":"Medical Science (医学)"}]},"item_7_text_24":{"attribute_name":"研究科・専攻","attribute_value_mlt":[{"subitem_text_value":"Department of Internal Medicine, Graduate School of Medicine (医学系研究科内科学専攻)"}]},"item_7_text_27":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_value":"博医第3279号"}]},"item_7_text_4":{"attribute_name":"著者所属","attribute_value_mlt":[{"subitem_text_value":"東京大学大学院医学系研究科内科学専攻"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"廣田, 信哲"}],"nameIdentifiers":[{"nameIdentifier":"8120","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","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":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","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":"タイトル","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":["280","356"],"pubdate":{"attribute_name":"公開日","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":"2022-12-19T03:45:02.124331+00:00"}