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Bardet–Biedl Syndrome proteins regulate cilia disassembly during tissue maturation

Cellular and Molecular Life Sciences volume 76, pages 757–775 (2019)Cite this article

Abstract

Primary cilia are conserved organelles that mediate cellular communication crucial for organogenesis and homeostasis in numerous tissues. The retinal pigment epithelium (RPE) is a ciliated monolayer in the eye that borders the retina and is vital for visual function. Maturation of the RPE is absolutely critical for visual function and the role of the primary cilium in this process has been largely ignored to date. We show that primary cilia are transiently present during RPE development and that as the RPE matures, primary cilia retract, and gene expression of ciliary disassembly components decline. We observe that ciliary-associated BBS proteins protect against HDAC6-mediated ciliary disassembly via their recruitment of Inversin to the base of the primary cilium. Inhibition of ciliary disassembly components was able to rescue ciliary length defects in BBS deficient cells. This consequently affects ciliary regulation of Wnt signaling. Our results shed light onto the mechanisms by which cilia-mediated signaling facilitates tissue maturation.

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Acknowledgments

This work was supported by the Alexander Von Humboldt Foundation and the Johannes Gutenberg University. The authors thank Uwe Wolfrum, Kerstin Nagel-Wolfrum and Anne Régnier-Vigouroux for abundant discussion and proofreading. We especially thank Elisabeth Sehn and Gabriele Stern-Schneider for expert technical assistance and Tina Sedmark for providing TEM specimens for analysis.

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Affiliations

  1. Cilia Cell Biology, Institute of Molecular Physiology, Johannes-Gutenberg University, 55128, Mainz, Germany

    Sarita Rani Patnaik, Viola Kretschmer, Lena Brücker, Sandra Schneider, Ann-Kathrin Volz & Helen Louise May-Simera

  2. Institute of Developmental Biology and Neurobiology, Johannes-Gutenberg University, 55128, Mainz, Germany

    Liliana del Rocio Oancea-Castillo

Authors
  1. Sarita Rani Patnaik
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  2. Viola Kretschmer
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  3. Lena Brücker
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  4. Sandra Schneider
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  7. Helen Louise May-Simera
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Contributions

SRP and HLM-S were responsible for conception and experimental design. SRP, VK, LB, A-KV, SS, LRO-C and HLM-S performed experiments. SRP and VK generated figures. SRP and HLM-S co-wrote the manuscript.

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Correspondence to Helen Louise May-Simera.

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Patnaik, S.R., Kretschmer, V., Brücker, L. et al. Bardet–Biedl Syndrome proteins regulate cilia disassembly during tissue maturation. Cell. Mol. Life Sci. 76, 757–775 (2019). https://doi.org/10.1007/s00018-018-2966-x

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  • DOI: https://doi.org/10.1007/s00018-018-2966-x

Keywords

  • Retinal dystrophy
  • Ciliopathy
  • Signaling pathways
  • Proteasomal degradation
  • Signaling inhibitors