Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse.

• Type of Material: Article
• Authors: Robert E Van Sciver, Emory University; Alyssa B Long, Emory University; Harrison G Katz, Emory University; Eduardo D Gigante, Emory University; Tamara Caspary, Emory University
• Language: English
• Date: 2023-05-15
• Publisher: bioRxiv
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2023.02.08.527739
• Title of Journal or Parent Work: bioRxiv
• Grant/Funding Information: This work was supported by the National Institutes of Health: Institutional Research and Career Development Award (IRACDA) K12GM000680 and F32DK127848 to REVS; T32NS096050, diversity supplement to R01NS090029 and F31NS106755 to EDG; the Summer Undergraduate Program in Emory Renal Research (SUPERR), R25DK101390 to HGK; and R01NS090029, R35GM122549, R35GM148416, and R01DK128902 to TC.
• Keywords: ARL3; ARL13B; renal cysts; GEF; cilia

Abstract

ARL13B is a small GTPase enriched in cilia. Deletion of Arl13b in mouse kidney results in renal cysts and an associated absence of primary cilia. Similarly, ablation of cilia leads to kidney cysts. To investigate whether ARL13B functions from within cilia to direct kidney development, we examined kidneys of mice expressing an engineered cilia-excluded ARL13B variant, ARL13B V358A . These mice retained renal cilia and developed cystic kidneys. Because ARL13B functions as a guanine nucleotide exchange factor (GEF) for ARL3, we examined kidneys of mice expressing an ARL13B variant that lacks ARL3 GEF activity, ARL13B R79Q . We found normal kidney development with no evidence of cysts in these mice. Taken together, our results show that ARL13B functions within cilia to inhibit renal cystogenesis during mouse development, and that this function does not depend on its role as a GEF for ARL3.