Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse
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Published on: December 2, 2014
Robert E Van Sciver1, Alyssa B Long1, Harrison G Katz2
1Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA, 30322, USA.
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, ARL13BV358A. 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, ARL13BR79Q. 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.
Insights
The small GTPase ARL13B normally prevents kidney cysts by functioning within cilia. Its role in inhibiting renal cystogenesis is independent of its guanine nucleotide exchange factor (GEF) activity for ARL3.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Primary cilia are crucial for kidney development.
- Loss of cilia or the small GTPase ARL13B leads to kidney cysts.
- ARL13B is localized to cilia and functions as a guanine nucleotide exchange factor (GEF) for ARL3.
Purpose of the Study:
- To investigate the role of ARL13B within cilia in kidney development.
- To determine if ARL13B's GEF activity for ARL3 is essential for its function in preventing renal cysts.
Main Methods:
- Generated transgenic mice expressing cilia-excluded (ARL13B V358A) and GEF-inactive (ARL13B R79Q) ARL13B variants.
- Examined kidney histology and presence of primary cilia in these mouse models.
- Assessed cyst formation and kidney development.
Main Results:
- Mice expressing cilia-excluded ARL13B V358A retained cilia but developed kidney cysts.
- Mice expressing GEF-inactive ARL13B R79Q showed normal kidney development without cysts.
- ARL13B functions within cilia to prevent renal cystogenesis.
Conclusions:
- ARL13B's function in inhibiting renal cystogenesis occurs within cilia.
- This protective role of ARL13B is independent of its GEF activity towards ARL3.
