{"id":143984,"date":"2022-08-14T19:20:49","date_gmt":"2022-08-15T00:20:49","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2022\/08\/human-cognition-enhancing-cord7-mutation-increases-active-zone-number-and-synaptic-release"},"modified":"2022-08-14T19:20:49","modified_gmt":"2022-08-15T00:20:49","slug":"human-cognition-enhancing-cord7-mutation-increases-active-zone-number-and-synaptic-release","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2022\/08\/human-cognition-enhancing-cord7-mutation-increases-active-zone-number-and-synaptic-release","title":{"rendered":"Human cognition-enhancing CORD7 mutation increases active zone number and synaptic release"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/human-cognition-enhancing-cord7-mutation-increases-active-zone-number-and-synaptic-release2.jpg\"><\/a><\/p>\n<p>This article tells of possible way to increase brain intelligence through a certain mutation which in theory could be altered for biological singularity like effects in the future.<\/p>\n<hr>\n<p>Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 3<sub>10<\/sub> helix of the C<sub>2<\/sub>A domain of RIMS1\/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca<sup>2+<\/sup>-triggered neurotransmitter release. How the CORD7 mutation affects synaptic function has remained unclear thus far. Here, we established <em>Drosophila melanogaster<\/em> as a disease model for clarifying the effects of the CORD7 mutation on RIM function and synaptic vesicle release.<\/p>\n<p>To this end, using protein expression and X-ray crystallography, we solved the molecular structure of the Drosophila C<sub>2<\/sub>A domain at 1.92 \u00c5 resolution and by comparison to its mammalian homolog ascertained that the location of the CORD7 mutation is structurally conserved in fly RIM. Further, CRISPR\/Cas9-assisted genomic engineering was employed for the generation of rim alleles encoding the R915H CORD7 exchange or R915E, R916E substitutions (fly numbering) to effect local charge reversal at the 3<sub>10<\/sub> helix. Through electrophysiological characterization by two-electrode voltage clamp and focal recordings we determined that the CORD7 mutation exerts a semi-dominant rather than a dominant effect on synaptic transmission resulting in faster, more efficient synaptic release and increased size of the readily releasable pool but decreased sensitivity for the fast calcium chelator BAPTA.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>This article tells of possible way to increase brain intelligence through a certain mutation which in theory could be altered for biological singularity like effects in the future. Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange [\u2026]<\/p>\n","protected":false},"author":513,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,38,47,64],"tags":[],"class_list":["post-143984","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-engineering","category-neuroscience","category-singularity"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/143984","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/513"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=143984"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/143984\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=143984"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=143984"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=143984"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}