{"created":"2023-06-19T10:43:47.294089+00:00","id":4105,"links":{},"metadata":{"_buckets":{"deposit":"2a66c0cf-4d93-46c3-80b8-f30e58c815e6"},"_deposit":{"created_by":11,"id":"4105","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4105"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004105","sets":["30:89:90"]},"author_link":["8531","6731","8530","7848","7847","6179","6731","7848","7847","6179"],"control_number":"4105","item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-12-28","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"5","bibliographicPageEnd":"585","bibliographicPageStart":"577","bibliographicVolumeNumber":"170","bibliographic_titles":[{"bibliographic_title":"Journal of biochemistry","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"清水, 昭男","creatorNameLang":"ja"},{"creatorName":"シミズ, アキオ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"6731","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"30769279","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=30769279"},{"nameIdentifier":"0000-0002-3393-6193","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0002-3393-6193"}]},{"creatorNames":[{"creatorName":"米野, 雅大","creatorNameLang":"ja"},{"creatorName":"コメノ, マサヒロ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"7848","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"佐藤, 朗","creatorNameLang":"ja"},{"creatorName":"サトウ, アキラ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"7847","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"70464302","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=70464302"}]},{"creatorNames":[{"creatorName":"扇田, 久和","creatorNameLang":"ja"},{"creatorName":"オウギタ, ヒサカズ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"6179","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"50379236","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=50379236"},{"nameIdentifier":"0000-0001-6750-1668","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0001-6750-1668"}]}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. R539Q) in TMEM168 was identified in patients with Brugada syndrome. This mutation reduced expression of cardiomyocyte sodium channel Nav1.5 via Nedd4-2 E3 ubiquitin ligase-induced ubiquitination and degradation. However, the detailed molecular mechanism provoked by the TMEM168 mutant remains unclear. Here, we demonstrated that small heat shock protein αB-crystallin, which can bind to Nav1.5 and Nedd4-2 and interfere with the association of both proteins, was strongly recruited from the cell surface to the perinuclear region because of the much higher affinity of αB-crystallin with the TMEM168 mutant than with wild-type TMEM168. Following knockdown of αB-crystallin in HL-1 cardiomyocytes, the interaction of Nav1.5 with Nedd4-2 was increased, despite the reduced expression of Nav1.5. Moreover, reduction of Nav1.5 expression by αB-crystallin knockdown was rescued in the presence of a proteasome inhibitor MG-132, suggesting the importance of the αB-crystallin-modulated ubiquitin-proteasome system for the stability of Nav1.5 expression. Collectively, the balance of molecular interactions among Nav1.5, Nedd4-2 and αB-crystallin plays a role in the regulation of cardiomyocyte cell surface expression of Nav1.5, and the TMEM168 mutant disturbs this balance, resulting in a decrease in Nav1.5 expression.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Oxford University Press","subitem_publisher_language":"en"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"34086898","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1093/jb/mvab066","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"©The Author(s) 2021.","subitem_rights_language":"en"},{"subitem_rights":"Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved","subitem_rights_language":"en"}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1756-2651","subitem_source_identifier_type":"EISSN"}]},"item_4_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"NGUYEN, Le Kim Chi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"8531","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"SHIMIZU, Akio","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"6731","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"30769279","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=30769279"},{"nameIdentifier":"0000-0002-3393-6193","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0002-3393-6193"}]},{"creatorNames":[{"creatorName":"SOH, Joanne Ern Chi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"8530","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"0000-0002-1940-860X","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0002-1940-860X"}]},{"creatorNames":[{"creatorName":"KOMENO, Masahiro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"7848","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"SATO, Akira","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"7847","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"70464302","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=70464302"}]},{"creatorNames":[{"creatorName":"OGITA, Hisakazu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"6179","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"50379236","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=50379236"},{"nameIdentifier":"0000-0001-6750-1668","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0001-6750-1668"}]}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Brugada syndrome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"heat shock protein","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"protein interaction","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"sodium channel","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ubiquitination","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics.","subitem_title_language":"en"}]},"item_type_id":"4","owner":"11","path":["90"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-02-01"},"publish_date":"2022-02-01","publish_status":"0","recid":"4105","relation_version_is_last":true,"title":["Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2024-05-07T04:46:12.903390+00:00"}