{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:26:12Z","timestamp":1787757972912,"version":"build-2784847793"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n \n Polycystic kidney disease (PKD) is the leading genetic cause of kidney failure, resulting in the accumulation of fluid filled cysts and gross enlargement of the kidney. Mutations in\n PKD1<\/jats:italic>\n or\n PKD2<\/jats:italic>\n , which encode ciliary polycystin proteins, are the most common cause of PKD. These proteins function in a cilia-dependent cyst activation (CDCA) pathway\u2013one that requires cilia for its pro-cystic function\u2013yet the molecular driver(s) of this pathway are unknown. ARL13B is a regulatory GTPase enriched in cilia and links to cystogenesis in the kidneys. ARL13B possesses guanine nucleotide exchange factor (GEF) activity for ARL3, another ARL with links to cilia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n We used two distinct\n Arl13b<\/jats:italic>\n mouse alleles to investigate whether ARL13B is a component of the CDCA pathway:\n Arl13b<\/jats:italic>\n V358A<\/jats:sup>\n encodes for enzymatically normal ARL13B that is undetectable in cilia, and\n Arl13b<\/jats:italic>\n R79Q<\/jats:sup>\n encodes for cilia-localized ARL13B lacking a residue critical for its ARL3 GEF activity. We used these alleles in a\n Pkd1<\/jats:italic>\n -deficient adult mouse model and investigated kidney morphology (H&E and cystic index analysis), physiology (blood urea nitrogen measurements), kidney fibrosis (picrosirius staining and \u03b1-smooth muscle actin levels), kidney injury (SOX9 immunofluorescent staining and quantification), and Wnt signaling (\u03b2-catenin and cyclin D1 protein levels).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n We found that loss of ciliary ARL13B or mutation of a single residue critical for its ARL3 GEF activity suppressed\n Pkd1<\/jats:italic>\n -dependent cysts. We observed reductions in kidney size, cystic index, and blood urea nitrogen. We also observed suppression of kidney fibrosis, kidney injury, and \u03b2-catenin and cyclin D1 protein levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Our results identified a subcellular location and mechanism driving\n Pkd1<\/jats:italic>\n -dependent cystogenesis in the kidneys. We demonstrated that expression of a critical residue for ARL13B\u2019s GEF activity specifically in cilia is a key mechanism of the CDCA pathway driving cystogenesis in the kidneys.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001238","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:00:23Z","timestamp":1787587223000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Ciliary ARL13B Drives Cystogenesis in the Kidney via Its GEF Activity"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1818-2661","authenticated-orcid":false,"given":"Robert E.","family":"Van Sciver","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA"},{"name":"Current address: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Heersink School of Medicine, 1918 University Boulevard, McCallum 227, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3037-2059","authenticated-orcid":false,"given":"Avery","family":"Forster","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA"},{"name":"Current address: Dana-Farber Cancer Institute, 375 Longwood Ave, LW-745, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7522-3397","authenticated-orcid":false,"given":"Leslie M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Current address: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Heersink School of Medicine, 1918 University Boulevard, McCallum 227, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-7589","authenticated-orcid":false,"given":"Tamara","family":"Caspary","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,24]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:00:25Z","timestamp":1787756425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001238","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"assertion":[{"value":"2025-11-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}