{"id":4815,"date":"2023-02-17T07:10:11","date_gmt":"2023-02-17T07:10:11","guid":{"rendered":"http:\/\/ionchanneltargets.com\/resource_library\/kcsa-lipid-bilayer-recordings-of-kcsa-channels-reconstituted-in-proteoliposomes\/"},"modified":"2023-02-17T07:10:12","modified_gmt":"2023-02-17T07:10:12","slug":"2010-the-g215r-mutation-in-the-cl%e2%88%92-h-antiporter-clc-7-found-in-ado-ii-osteopetrosis-does-not-abolish-function-but-causes-a-severe-trafficking-defect","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2010-the-g215r-mutation-in-the-cl%e2%88%92-h-antiporter-clc-7-found-in-ado-ii-osteopetrosis-does-not-abolish-function-but-causes-a-severe-trafficking-defect\/","title":{"rendered":"2010 &#8211; The G215R Mutation in the Cl\u2212\/H+-Antiporter ClC-7 Found in ADO II Osteopetrosis Does Not Abolish Function but Causes a Severe Trafficking Defect"},"content":{"rendered":"<p>BACKGROUND:ClC-7 is a ubiquitous transporter which is broadly expressed in mammalian tissues. It is implied in the pathogenesis of lysosomal storage disease and osteopetrosis. Because of its endosomal\/lysosomal localization it is still poorly characterized.METHODOLOGY\/PRINCIPAL FINDINGS:An electrophysiological characterization of rat ClC-7 using solid-supported membrane-based electrophysiology is presented. The measured currents show the characteristics of ClC-7 and confirm its function as a Cl-\/H+-antiporter. We have used rat ClC-7 in CHO cells as a model system to investigate the functionality and cellular localization of the wt transporter and its variant G213R ClC-7 which is the analogue of human G215R ClC-7 responsible for autosomal dominant osteopetrosis type II. Our study shows that rat G213R ClC-7 is functional but has a localization defect in CHO cells which prevents it from being correctly targeted to the lysosomal membrane. The electrophysiological assay is tested as a tool for drug discovery. The assay is validated with a number of drug candidates. It is shown that ClC-7 is inhibited by DIDS, NPPB and NS5818 at micromolar concentrations.CONCLUSIONS\/SIGNIFICANCE:It is suggested that the scenario found in the CHO model system also applies to the human transporter and that mislocalization rather than impaired functionality of G215R ClC-7 is the primary cause of the related autosomal dominant osteopetrosis type II. Furthermore, the robust solid-supported membrane-based electrophysiological assay is proposed for rapid screening for potential ClC-7 inhibitors which are discussed for treatment of osteoporosis.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[50,108],"therapeutic_areas":[],"target_categories":[61,60],"target_families":[343,372],"targets":[139],"resource_keyword":[],"class_list":["post-4815","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-ion-channels","application_areas-transporters","target_categories-voltage-gated-ion-channels","target_categories-transporters","target_families-exchanger","target_families-clc-channels","targets-clc"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/4815","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=4815"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=4815"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=4815"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=4815"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=4815"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=4815"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=4815"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=4815"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=4815"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}