Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse

Sciver, Robert E. Van; Long, Alyssa; Katz, Harrison; Gigante, Eduardo D.; Caspary, Tamara

doi:10.1101/2023.02.08.527739

Cited by 1 publication

(1 citation statement)

References 69 publications

(122 reference statements)

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“…We recently reported that Arl13b V358A/V358A mice develop kidney cysts 37 . Small cysts are visible at weaning age and become progressively larger by ~4 months of age.…”

Section: Arl13b V358a/v358a Mice Weigh Significantly More Than Contro...mentioning

confidence: 99%

Ciliary ARL13B prevents obesity in mice

Terry

Gigante

Alexandre

et al. 2023

Preprint

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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,V358Awhich 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 theArl13bV358A/V358Amodel. In addition to its GTPase function, ARL13B acts as a guanine nucleotide exchange factor (GEF) for ARL3. To test whether the GEF activity is required to regulate body weight, we analyzed the body weight of mice expressing ARL13BR79Q, 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, ARL13BV358A, enables us to define the cilia-specific role of ARL13B in regulating energy homeostasis.

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“…We recently reported that Arl13b V358A/V358A mice develop kidney cysts 37 . Small cysts are visible at weaning age and become progressively larger by ~4 months of age.…”

Section: Arl13b V358a/v358a Mice Weigh Significantly More Than Contro...mentioning

confidence: 99%