{"id":5265,"date":"2023-05-12T12:13:20","date_gmt":"2023-05-12T17:13:20","guid":{"rendered":"https:\/\/irrf.org\/?p=5265"},"modified":"2023-10-04T12:37:51","modified_gmt":"2023-10-04T17:37:51","slug":"ubiquitylation-of-bbsome-is-required-for-ciliary-assembly-and-signaling","status":"publish","type":"post","link":"https:\/\/irrf.org\/ubiquitylation-of-bbsome-is-required-for-ciliary-assembly-and-signaling\/","title":{"rendered":"Ubiquitylation of BBSome is required for ciliary assembly and signaling"},"content":{"rendered":"\r\n<p><strong>PROJECT TITLE: <\/strong><em>Ubiquitylation of BBSome is required for ciliary assembly and signaling.<\/em><\/p>\r\n<ul>\r\n<li>\r\n<p class=\"p1\">Francesco Chiuso, Rossella delle Donne, Giuliana Giamundo, Laura Rinaldi, Domenica Borzacchiello, Federica Moraca, Daniela Intartaglia, Rosa Iannuci, Emanuela Senatore, Luca Lignitto, Carrodo Garbi, Paolo Conflitti, Bruno Catalanotti, <b>Ivan Conte<\/b>, &amp; Antonio Feliciello<\/p>\r\n<\/li>\r\n<\/ul>\r\n<figure id=\"attachment_5155\" aria-describedby=\"caption-attachment-5155\" style=\"width: 114px\" class=\"wp-caption alignleft\"><img decoding=\"async\" class=\"wp-image-5155 size-thumbnail\" src=\"https:\/\/irrf.org\/wp-content\/uploads\/2023\/05\/embopress-Ivan-Conte-2023-114x150.jpg\" alt=\"Cover image of EMBO reports, Volume 24 Issue 4 | 5, April 2023\" width=\"114\" height=\"150\" srcset=\"https:\/\/irrf.org\/wp-content\/uploads\/2023\/05\/embopress-Ivan-Conte-2023-114x150.jpg 114w, https:\/\/irrf.org\/wp-content\/uploads\/2023\/05\/embopress-Ivan-Conte-2023-228x300.jpg 228w, https:\/\/irrf.org\/wp-content\/uploads\/2023\/05\/embopress-Ivan-Conte-2023.jpg 761w\" sizes=\"(max-width: 114px) 100vw, 114px\" \/><figcaption id=\"caption-attachment-5155\" class=\"wp-caption-text\">EMBO reports, Volume 24 Issue 4 | 5, April 2023<\/figcaption><\/figure>\r\n<p><strong>ABSTRACT: <\/strong>Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, renal abnormalities, postaxial polydactyly, and developmental defects.<span class=\"Apple-converted-space\">\u00a0 <\/span>Genes mutated in BBS encode for components and regulators of the BBSome, an octomeric complex that controls the trafficking of cargos and receptors within the primary cilium.<span class=\"Apple-converted-space\">\u00a0 <\/span>Although both structure and function of the BBSome have been extensively studied, the impact of ubiquitin signaling on BBSome is largely unknown.<span class=\"Apple-converted-space\">\u00a0 <\/span>We identify the E3 ubiquitin ligase PJA2 as a novel resident of the ciliary compartment and regulator of the BBSome.<span class=\"Apple-converted-space\">\u00a0 <\/span>Upon GPCR-cAMP stimulation, PJA2 ubiquitylates BBSome subunits.<span class=\"Apple-converted-space\">\u00a0 <\/span>We demonstrate that ubiquitylation of BBS1 at lysine 143 increases the stability of the BBSome and promotes its binding to BBS3, an Arf-like GTPase protein controlling the targeting of the BBSome to the ciliary membrane.<span class=\"Apple-converted-space\">\u00a0 <\/span>Downregulation of PJA2 or expression of a ubiquitylation-defective BBS1 mutant (BBS1<span class=\"s1\"><sup>K143R<\/sup><\/span>) affects the trafficking of G-protein-coupled receptors (GPCRs) and Shh-dependent gene transcription.<span class=\"Apple-converted-space\">\u00a0 <\/span>Expression of BBS1<span class=\"s1\"><sup>K143R <\/sup><\/span><i>in vivo<\/i> impairs cilium formation, embryonic development, and photoreceptors\u2019 morphogenesis, thus recapitulating the BBS phenotype in the medaka fish model. <strong>ACCESS ARTICLE: <\/strong><a href=\"http:\/\/www.embopress.org\/doi\/full\/10.15252\/embr.202255571\" target=\"_blank\" rel=\"noopener\">Click this link<\/a><\/p>\r\n<p class=\"p1\"><b>Author Contributions:<span class=\"Apple-converted-space\">\u00a0 <\/span>Ivan Conte, PhD<\/b><strong>: <\/strong>Supervision, funding acquisition; investigation; writing \u2013 original draft; writing \u2013 review and editing.<\/p>\r\n<p class=\"p1\"><i>This study was conducted with IRRF Funds: Ivan Conte, PhD<\/i><\/p>\r\n\r\n\r\n","protected":false},"excerpt":{"rendered":"<p>PROJECT TITLE: Ubiquitylation of BBSome is required for ciliary assembly and signaling. Francesco Chiuso, Rossella delle Donne, Giuliana Giamundo, Laura Rinaldi, Domenica Borzacchiello, Federica Moraca, Daniela Intartaglia, Rosa Iannuci, Emanuela Senatore, Luca Lignitto, Carrodo Garbi, Paolo Conflitti, Bruno Catalanotti, Ivan Conte, &amp; Antonio Feliciello ABSTRACT: Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":5154,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[328],"tags":[],"_links":{"self":[{"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/posts\/5265"}],"collection":[{"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/comments?post=5265"}],"version-history":[{"count":2,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/posts\/5265\/revisions"}],"predecessor-version":[{"id":5269,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/posts\/5265\/revisions\/5269"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/media\/5154"}],"wp:attachment":[{"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/media?parent=5265"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/categories?post=5265"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/irrf.org\/wp-json\/wp\/v2\/tags?post=5265"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}