Rabl2 GTP hydrolysis licenses BBSome‐mediated export to fine‐tune ciliary signaling |
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| Authors: | Shichao Duan Hao Li Yirong Zhang Suming Yang Yawen Chen Benhua Qiu Cheng Huang Juan Wang Jinsong Li Xueliang Zhu Xiumin Yan |
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| Institution: | 1. State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai China ; 2. University of Chinese Academy of Sciences, Beijing China ; 3. Department of Pathology, First Affiliated Hospital of Zhengzhou University, Zhengzhou China ; 4. School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou China |
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| Abstract: | Cilia of higher animals sense various environmental stimuli. Proper ciliary signaling requires appropriate extent of BBSome‐mediated export of membrane receptors across ciliary barrier transition zone (TZ) through retrograde intraflagellar transport (IFT) machinery. How the barrier passage is controlled, however, remains unknown. Here, we show that small GTPase Rabl2 functions as a molecular switch for the outward TZ passage. Rabl2‐GTP enters cilia by binding to IFT‐B complex. Its GTP hydrolysis enables the outward TZ passage of the BBSome and its cargos with retrograde IFT machinery, whereas its persistent association leads to their shedding from IFT‐B during the passing process and consequently ciliary retention. Rabl2 deficiency or expression of a GTP‐locked mutant impairs the ciliary hedgehog signaling without interfering with ciliation and respectively results in different spectrums of mouse developmental disorders. We propose that the switch role of Rabl2 ensures proper turnover of the BBSome and ciliary membrane receptors to fine‐tune cilia‐dependent signaling for normal embryonic development and organismic homeostasis. |
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| Keywords: | BBSome ciliary signaling intraflagellar transport small GTPase transition zone |
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