{"id":976,"date":"2020-02-21T16:56:33","date_gmt":"2020-02-21T09:26:33","guid":{"rendered":"http:\/\/bioactivecompoundlibrary.com\/?p=976"},"modified":"2022-01-11T17:17:30","modified_gmt":"2022-01-11T09:47:30","slug":"previous-studies-show-enrichment-a-actinin-2-rat-forebrain-post-synaptic-density-fractions","status":"publish","type":"post","link":"http:\/\/bioactivecompoundlibrary.com\/index.php\/2020\/02\/21\/previous-studies-show-enrichment-a-actinin-2-rat-forebrain-post-synaptic-density-fractions\/","title":{"rendered":"Whereas previous studies show enrichment of a-actinin-2 in rat forebrain post-synaptic density fractions"},"content":{"rendered":"

The N-terminal actin binding domain is followed by four tandem spectrin repeats and a calmodulin-like domain, that determines each isoform\u2019s calcium sensitivity, at its Cterminus. Although three of the four a-actinin isoforms, aactinin-1, -2, and -4, have been identified in rat PSD fractions by mass spectrometry and RT-PCR of cultured hippocampal neurons, immunofluorescence and electron microscopy studies have shown specific enrichment of a-actinin-2 in the PSD of excitatory synapses in pyramidal neurons of the cortex and hippocampus. In addition to cross-linking actin filaments, a-actinin interacts with several membrane-associated proteins, including integrins, acatenin, and the L-type Ca2+ channel Cav1.2, and through these interactions a-actinin is thought to couple these molecules to actin filaments. In vitro binding assays suggest a-actinin-2 interacts directly with the NR1 and NR2B subunits of the NMDA receptor. In vitro studies also suggest a-actinin-2 binds to densin-180 to form a ternary complex with CaMKIIa and NR2B. These observations are supported by studies in HEK293 cells, in which a-actinin-2 targets CaMKIIa to F-actin and enhances the interaction between CaMKIIa and NR2B. These putative interactions suggest a-actinin-2 could interpret signals and mediate interactions between PSD components and the actin cytoskeleton, and thus play a pivotal role in post-synaptic organization. a-Actinin regulation and function in spines is poorly understood and relies largely on in vitro binding interactions or studies in nonneuronal cells. PtdInsP2, PIP2, binds to the actin-binding domain of a-actinin-2 and tethers it to the plasma membrane, a function thought to maintain the open state of the NMDA receptor. Neurons expressing an a-actinin-2 mutant unable to interact with PIP2 display significantly reduced peak and steadystate NMDA current compared to neurons expressing wild-type aactinin-2. In one study, overexpression of a-actinin-2 increased the length and density of dendritic protrusions in cultured hippocampal neurons, suggesting a role in determining spine morphology. To ascertain a biological function for a-actinin-2 in spines, we knocked down a-actinin-2 in hippocampal neurons via short interfering RNA. We find that loss of a-actinin-2 increases spine density and the presence of filopodia-like spines that lack a PSD. These immature spines do not form synapses and therefore do not mature in response to chemical stimulation. We further show the Ca2+-insensitive EF-hand motif in a-actinin-2 is critical for its role in spine morphogenesis and PSD organization. Expression of either a-actinin-4 or a Ca2+-sensitive a-actinin-2 mutant does not rescue spine morphology and PSD assembly in neurons lacking endogenous a-actinin-2. However, expression of a Ca2+-insensitive a-actinin-4 mutant does rescue PSD organization. These studies suggest a-actinin-2 BEZ235<\/a> re-organizes the actin cytoskeleton in filopodialike dendritic protrusions to promote assembly of the PSD and mediate its transition to a mature, mushroom-shaped morphology.<\/p>\n","protected":false},"excerpt":{"rendered":"

The N-terminal actin binding domain is followed by four tandem spectrin repeats and a calmodulin-like domain, that determines each isoform\u2019s calcium sensitivity, at its Cterminus. Although three of the four a-actinin isoforms, aactinin-1, -2, and -4, have been identified in rat PSD fractions by mass spectrometry and RT-PCR of cultured hippocampal neurons, immunofluorescence and electron… Continue reading Whereas previous studies show enrichment of a-actinin-2 in rat forebrain post-synaptic density fractions<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/976"}],"collection":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/comments?post=976"}],"version-history":[{"count":1,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/976\/revisions"}],"predecessor-version":[{"id":977,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/976\/revisions\/977"}],"wp:attachment":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/media?parent=976"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/categories?post=976"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/tags?post=976"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}