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Rabl2 GTP hydrolysis licenses BBSome‐mediated export to fine‐tune ciliary signaling
Author(s) -
Duan Shichao,
Li Hao,
Zhang Yirong,
Yang Suming,
Chen Yawen,
Qiu Benhua,
Huang Cheng,
Wang Juan,
Li Jinsong,
Zhu Xueliang,
Yan Xiumin
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105499
Subject(s) - cilium , microbiology and biotechnology , biology , intraflagellar transport , gtpase , smoothened , gtp' , signal transduction , mutant , hedgehog signaling pathway , biochemistry , gene , enzyme
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.