{"id":17170,"date":"2025-04-15T08:42:13","date_gmt":"2025-04-15T08:42:13","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=17170"},"modified":"2025-04-15T08:42:13","modified_gmt":"2025-04-15T08:42:13","slug":"2025-pip2-mediated-oligomerization-of-the-endosomal-sodium-proton-exchanger-nhe9","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2025-pip2-mediated-oligomerization-of-the-endosomal-sodium-proton-exchanger-nhe9\/","title":{"rendered":"2025 &#8211; PIP2-mediated oligomerization of the endosomal sodium\/proton exchanger NHE9"},"content":{"rendered":"<p>The strict exchange of Na<sup>+<\/sup>\u00a0for H<sup>+<\/sup>\u00a0ions across cell membranes is a reaction carried out in almost every cell. Na<sup>+<\/sup>\/H<sup>+<\/sup>\u00a0exchangers that perform this task are physiological homodimers, and whilst the ion transporting domain is highly conserved, their dimerization differs. The Na<sup>+<\/sup>\/H<sup>+<\/sup>\u00a0exchanger NhaA from\u00a0<i>Escherichia coli<\/i>\u00a0has a weak dimerization interface mediated by a \u03b2-hairpin domain and with dimer retention dependent on cardiolipin. Similarly, organellar Na<sup>+<\/sup>\/H<sup>+<\/sup>\u00a0exchangers NHE6, NHE7 and NHE9 also contain \u03b2-hairpin domains and recent analysis of\u00a0<i>Equus caballus<\/i>\u00a0NHE9 indicated PIP<sub>2<\/sub>\u00a0lipids could bind at the dimer interface. However, structural validation of the predicted lipid-mediated oligomerization has been lacking. Here, we report cryo-EM structures of\u00a0<i>E. coli<\/i>\u00a0NhaA and\u00a0<i>E. caballus<\/i>\u00a0NHE9 in complex with cardiolipin and phosphatidylinositol-3,5-bisphosphate PI(3,5)P<sub>2<\/sub>\u00a0lipids binding at their respective dimer interfaces. We further show how the endosomal specific PI(3,5)P<sub>2<\/sub>\u00a0lipid stabilizes the NHE9 homodimer and enhances transport activity. Indeed, we show that NHE9 is active in endosomes, but not at the plasma membrane where the PI(3,5)P<sub>2<\/sub>\u00a0lipid is absent. Thus, specific lipids can regulate Na<sup>+<\/sup>\/H<sup>+<\/sup>\u00a0exchange activity by stabilizing dimerization in response to either cell specific cues or upon trafficking to their correct membrane location.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[76,108],"therapeutic_areas":[143],"target_categories":[60],"target_families":[503],"targets":[483,506],"resource_keyword":[],"class_list":["post-17170","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-drug-discovery","application_areas-transporters","therapeutic_areas-assay-development-and-validation","target_categories-transporters","target_families-solute-carrier-family-slc","targets-nhaa","targets-nhe9-slc9a9"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/17170","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=17170"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=17170"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=17170"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=17170"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=17170"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=17170"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=17170"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=17170"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=17170"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}