{"id":6365,"date":"2023-02-17T06:57:16","date_gmt":"2023-02-17T06:57:16","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-a-p2rx7-single-nucleotide-polymorphism-haplotype-promotes-exon-7-and-8-skipping-and-disrupts-receptor-function\/"},"modified":"2023-02-17T06:57:16","modified_gmt":"2023-02-17T06:57:16","slug":"2020-a-p2rx7-single-nucleotide-polymorphism-haplotype-promotes-exon-7-and-8-skipping-and-disrupts-receptor-function","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2020-a-p2rx7-single-nucleotide-polymorphism-haplotype-promotes-exon-7-and-8-skipping-and-disrupts-receptor-function\/","title":{"rendered":"2020 &#8211; A P2RX7 single nucleotide polymorphism haplotype promotes exon 7 and 8 skipping and disrupts receptor function"},"content":{"rendered":"<p>P2X7 is an ATP\u2010gated membrane ion channel that is expressed by multiple cell types. Brief exposure to ATP induces the opening of a nonselective cation channel; while repeated or prolonged exposure induces formation of a transmembrane pore. This process may be partially regulated by alternative splicing of full\u2010length\u00a0P2RX7A\u00a0pre\u2010mRNA, producing isoforms that delete or retain functional domains. Here, we report cloning and expression of a novel\u00a0P2RX7\u00a0splice variant,\u00a0P2RX7L, that is, characterized by skipping of exons 7 and 8. In HEK 293 cells, expression of\u00a0P2RX7L\u00a0produces a protein isoform, P2X7L, that forms a heteromer with P2X7A. A haplotype defined by six single nucleotide polymorphisms (SNPs) (rs208307, rs208306, rs36144485, rs208308, rs208309, and rs373655596) promotes allele\u2010specific alternative splicing, increasing mRNA levels of\u00a0P2RX7L\u00a0and another isoform,\u00a0P2RX7E, which in addition has a truncated C\u2010terminus. Skipping of exons 7 and 8 is predicted to delete critical amino acids in the ATP\u2010binding site. P2X7L\u2010transfected HEK 293 cells have phagocytic but not channel, pore, or membrane\u2010blebbing function, and double\u2010transfected P2X7L and P2X7A cells have reduced pore function. Heteromeric receptor complexes of P2X7A and P2X7L are predicted to have reduced numbers of ATP\u2010binding sites, which potentially alters receptor function compared to homomeric P2X7A complexes.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[337],"target_families":[358],"targets":[226],"resource_keyword":[],"class_list":["post-6365","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","target_categories-ligand-gated-ion-channels","target_families-p2x-receptors","targets-p2x7"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6365","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=6365"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6365"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6365"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6365"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6365"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6365"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6365"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6365"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6365"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}