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Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of\n                    <jats:italic>Dlg1<\/jats:italic>\n                    in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.\n                  <\/jats:p>","DOI":"10.1038\/s44319-024-00170-1","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T11:02:04Z","timestamp":1717758124000},"page":"3040-3063","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5192-0151","authenticated-orcid":false,"given":"Csenge K","family":"Rezi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam G","family":"Aslanyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-3020","authenticated-orcid":false,"given":"Gaurav D","family":"Diwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9942-1424","authenticated-orcid":false,"given":"Mohamed","family":"Chamlali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9681-2908","authenticated-orcid":false,"given":"Katrin","family":"Junger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Anvarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-7220","authenticated-orcid":false,"given":"Esben","family":"Lorentzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kleo B","family":"Pauly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Afshar-Bahadori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo FA","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-9772","authenticated-orcid":false,"given":"Feng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Tosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-304X","authenticated-orcid":false,"given":"S\u00f8ren T","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-7714","authenticated-orcid":false,"given":"Stine F","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Str\u00f8mgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-4717","authenticated-orcid":false,"given":"Robert B","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H","family":"Miner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-7464","authenticated-orcid":false,"given":"Moe R","family":"Mahjoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Boldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-8163","authenticated-orcid":false,"given":"Ronald","family":"Roepman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-3758","authenticated-orcid":false,"given":"Lotte B","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"170_CR1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1681\/ASN.2012111074","volume":"24","author":"S Ahn","year":"2013","unstructured":"Ahn S, Kim Y, Kim ST, Swat W, Miner JH (2013) Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development. 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