| Autor: |
Terry TT; Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA., Gigante ED; Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA.; Graduate Program in Neuroscience, Laney Graduate School, Emory University, 201 Dowman Dr., Atlanta, GA 30307, USA.; Present address: Department of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA., Alexandre CM; Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143., Brewer KM; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Engle SE; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Yue X; Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143., Berbari NF; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Vaisse C; Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143., Caspary T; Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA. |
| Abstrakt: |
Cilia are near ubiquitous small, cellular appendages critical for cell-to-cell communication. As such, they are involved in diverse developmental and homeostatic processes, including energy homeostasis. ARL13B is a regulatory GTPase highly enriched in cilia. Mice expressing an engineered ARL13B variant, ARL13B V358A which retains normal biochemical activity, display no detectable ciliary ARL13B. Surprisingly, these mice become obese. Here, we measured body weight, food intake, and blood glucose levels to reveal these mice display hyperphagia and metabolic defects. We showed that ARL13B normally localizes to cilia of neurons in specific brain regions and pancreatic cells but is excluded from these cilia in the Arl13b V358A/V358A model. In addition to its GTPase function, ARL13B acts as a guanine nucleotide exchange factor (GEF) for ARL3. To test whether ARL13B's GEF activity is required to regulate body weight, we analyzed the body weight of mice expressing ARL13B R79Q , a variant that lacks ARL13B GEF activity for ARL3. We found no difference in body weight. Taken together, our results show that ARL13B functions within cilia to control body weight and that this function does not depend on its role as a GEF for ARL3. Controlling the subcellular localization of ARL13B in the engineered mouse model, ARL13B V358A , enables us to define the cilia-specific role of ARL13B in regulating energy homeostasis. |
