{"id":73669,"date":"2022-11-02T16:30:11","date_gmt":"2022-11-02T07:30:11","guid":{"rendered":"https:\/\/www.waseda.jp\/inst\/research\/?p=73669"},"modified":"2022-11-02T16:30:11","modified_gmt":"2022-11-02T07:30:11","slug":"inka2a-novel-pak4-inhibitorregulates-actin-dynamics-in-neuronal-development%ef%bc%88published-in-plos-genetics-october-2022%ef%bc%89","status":"publish","type":"post","link":"https:\/\/www.waseda.jp\/inst\/research\/news\/73669","title":{"rendered":"Inka2,a novel Pak4 inhibitor,regulates actin dynamics in neuronal development\uff08Published in PLoS Genetics, October 2022\uff09"},"content":{"rendered":"<table class=\"table table-bordered table-colored-tbhd\" style=\"height: 550px; width: 100%; border-collapse: collapse; border-style: solid;\" border=\"1\">\n<tbody>\n<tr style=\"height: 78px;\">\n<td style=\"width: 16.7893%; height: 78px;\">Journal Title<br \/>\n\/\u63b2\u8f09\u30b8\u30e3\u30fc\u30ca\u30eb\u540d<\/td>\n<td style=\"width: 71.3712%; height: 78px;\">PLoS Genetics<\/td>\n<\/tr>\n<tr style=\"height: 65px;\">\n<td style=\"width: 16.7893%; height: 80px;\">Publication Year and Month<br \/>\n\/\u63b2\u8f09\u5e74\u6708<\/td>\n<td style=\"width: 71.3712%; height: 80px;\">October, 2022<\/td>\n<\/tr>\n<tr style=\"height: 55px;\">\n<td style=\"width: 16.7893%; height: 79px;\">Paper Title<br \/>\n\/\u8ad6\u6587\u30bf\u30a4\u30c8\u30eb<\/td>\n<td style=\"width: 71.3712%; height: 79px;\">Inka2,a novel Pak4 inhibitor,regulates actin dynamics in neuronal development<\/td>\n<\/tr>\n<tr style=\"height: 85px;\">\n<td style=\"width: 16.7893%; height: 85px;\">DOI<br \/>\n\/\u8ad6\u6587DOI<\/td>\n<td style=\"width: 71.3712%; height: 85px;\"><a href=\"https:\/\/doi.org\/10.1371\/journal.pgen.1010438\">10.1371\/journal.pgen.1010438<\/a><\/td>\n<\/tr>\n<tr style=\"height: 59px;\">\n<td style=\"width: 16.7893%; height: 80px;\">\u00a0Author of Waseda University<br \/>\n\/\u672c\u5b66\u306e\u8457\u8005<\/td>\n<td style=\"width: 71.3712%; height: 80px;\">SAKAKIBARA, Shinichi(Professor, Faculty of Human Sciences, School of Human Sciences):Corresponding Author<\/td>\n<\/tr>\n<tr style=\"height: 68px;\">\n<td style=\"width: 16.7893%; height: 86px;\">Related Websites<br \/>\n\/\u95a2\u9023Web<\/td>\n<td style=\"width: 71.3712%; height: 86px;\">&#8211;<\/td>\n<\/tr>\n<tr style=\"height: 138px;\">\n<td style=\"width: 16.7893%; height: 148px;\">Abstract<br \/>\n\/\u6284\u9332<\/td>\n<td style=\"width: 71.3712%; height: 148px;\">The actin filament is a fundamental part of the cytoskeleton defining cell morphology and regulating various physiological processes, including filopodia formation and dendritic spinogenesis of neurons. Serine\/threonine-protein kinase Pak4, an essential effector, links Rho GTPases to control actin polymerization. Previously, we identified the\u00a0<em>Inka2<\/em>\u00a0gene, a novel mammalian protein exhibiting sequence similarity to\u00a0<em>Inka1<\/em>, which serves as a possible inhibitor for Pak4. Although\u00a0<em>Inka2<\/em>\u00a0is dominantly expressed in the nervous system and involved in focal-adhesion dynamics, its molecular role remains unclear. Here, we found that Inka2-iBox directly binds to Pak4 catalytic domain to suppress actin polymerization. Inka2 promoted actin depolymerization and inhibited the formation of cellular protrusion caused by Pak4 activation. We further generated the conditional knockout mice of the\u00a0<em>Inka2<\/em>\u00a0gene. The beta-galactosidase reporter indicated the preferential\u00a0<em>Inka2<\/em>\u00a0expression in the dorsal forebrain neurons. Cortical pyramidal neurons of\u00a0<em>Inka2<\/em><sup>-\/-<\/sup>\u00a0mice exhibited decreased density and aberrant morphology of dendritic spines with marked activation\/phosphorylation of downstream molecules of Pak4 signal cascade, including LIMK and Cofilin. These results uncovered the unexpected function of endogenous Pak4 inhibitor in neurons. Unlike\u00a0<em>Inka1<\/em>,\u00a0<em>Inka2<\/em>\u00a0is a critical mediator for actin reorganization required for dendritic spine development.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Journal Title \/\u63b2\u8f09\u30b8\u30e3\u30fc\u30ca\u30eb\u540d PLoS Genetics Publication Year and Month \/\u63b2\u8f09\u5e74\u6708 October, 2022 Paper Title \/\u8ad6\u6587\u30bf\u30a4\u30c8\u30eb Inka2 [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[],"tags":[218,217],"class_list":["post-73669","post","type-post","status-publish","format-standard","hentry","tag-impact-en","tag-impact"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/posts\/73669","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/comments?post=73669"}],"version-history":[{"count":1,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/posts\/73669\/revisions"}],"predecessor-version":[{"id":73670,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/posts\/73669\/revisions\/73670"}],"wp:attachment":[{"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/media?parent=73669"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/categories?post=73669"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.waseda.jp\/inst\/research\/wp-json\/wp\/v2\/tags?post=73669"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}