{"id":382,"date":"2021-01-16T23:38:02","date_gmt":"2021-01-16T18:38:02","guid":{"rendered":"http:\/\/curesteps.org\/SCI\/?p=382"},"modified":"2021-01-16T23:38:05","modified_gmt":"2021-01-16T18:38:05","slug":"gsk3-crmp2-signaling-mediates-axonal-regeneration-induced-by-pten-knockout","status":"publish","type":"post","link":"http:\/\/curesteps.org\/SCI\/gsk3-crmp2-signaling-mediates-axonal-regeneration-induced-by-pten-knockout\/","title":{"rendered":"GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout"},"content":{"rendered":"\n<p><a href=\"https:\/\/www.nature.com\/articles\/s42003-019-0524-1\">Link<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"Abs1\">Abstract<\/h2>\n\n\n\n<p>Knockout of phosphatase and tensin homolog (PTEN<sup>\u2212\/\u2212<\/sup>) is neuroprotective and promotes axon regeneration in mature neurons. Elevation of mTOR activity in injured neurons has been proposed as the primary underlying mechanism. Here we demonstrate that PTEN<sup>\u2212\/\u2212<\/sup>&nbsp;also abrogates the inhibitory activity of GSK3 on collapsin response mediator protein 2 (CRMP2) in retinal ganglion cell (RGC) axons. Moreover, maintenance of GSK3 activity in&nbsp;<em>Gsk3<\/em><sup><em>S\/A<\/em><\/sup>&nbsp;knockin mice significantly compromised PTEN<sup>\u2212\/\u2212<\/sup>-mediated optic nerve regeneration as well as the activity of CRMP2, and to a lesser extent, mTOR. These GSK3<sup>S\/A<\/sup>&nbsp;mediated negative effects on regeneration were rescued by viral expression of constitutively active CRMP2<sup>T\/A<\/sup>, despite decreased mTOR activation.&nbsp;<em>Gsk3<\/em><sup><em>S\/A<\/em><\/sup>&nbsp;knockin or CRMP2 inhibition also decreased PTEN<sup>\u2212\/\u2212<\/sup>&nbsp;mediated neurite growth of RGCs in culture and disinhibition towards CNS myelin. Thus, the GSK3\/CRMP2 pathway is essential for PTEN<sup>\u2212\/\u2212<\/sup>&nbsp;mediated axon regeneration. These new mechanistic insights may help to find novel strategies to promote axon regeneration.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Link Abstract Knockout of phosphatase and tensin homolog (PTEN\u2212\/\u2212) is neuroprotective and promotes axon regeneration in mature neurons. Elevation of mTOR activity in injured neurons has been proposed as the primary underlying mechanism. Here we demonstrate that PTEN\u2212\/\u2212&nbsp;also abrogates the inhibitory activity of GSK3 on collapsin response mediator protein 2 (CRMP2) in retinal ganglion cell [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[22],"class_list":["post-382","post","type-post","status-publish","format-standard","hentry","category-growth-factors","tag-growth-factors"],"_links":{"self":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/382","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/comments?post=382"}],"version-history":[{"count":1,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/382\/revisions"}],"predecessor-version":[{"id":383,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/382\/revisions\/383"}],"wp:attachment":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/media?parent=382"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/categories?post=382"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/tags?post=382"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}