Van Sciver Robert E, Long Alyssa B, Katz Harrison G, Gigante Eduardo D, Caspary Tamara
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA.
Present address: Department of Biology, Brown University, Providence, RI 02912, USA.
bioRxiv. 2023 May 15:2023.02.08.527739. doi: 10.1101/2023.02.08.527739.
ARL13B is a small GTPase enriched in cilia. Deletion of 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. 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. 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.
ARL13B是一种在纤毛中富集的小GTP酶。在小鼠肾脏中缺失该蛋白会导致肾囊肿以及原发性纤毛的缺失。同样，纤毛的消融也会导致肾囊肿。为了研究ARL13B是否在纤毛内发挥作用以指导肾脏发育，我们检查了表达工程化的排除在纤毛外的ARL13B变体（ARL13B）的小鼠的肾脏。这些小鼠保留了肾纤毛并发展出多囊肾。由于ARL13B作为ARL3的鸟嘌呤核苷酸交换因子（GEF）发挥作用，我们检查了表达缺乏ARL3 GEF活性的ARL13B变体（ARL13B）的小鼠的肾脏。我们发现这些小鼠的肾脏发育正常，没有囊肿的迹象。综上所述，我们的结果表明，ARL13B在纤毛内发挥作用以抑制小鼠发育过程中的肾囊肿形成，并且该功能不依赖于其作为ARL3的GEF的作用。
