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Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry.


ABSTRACT: Compositions of proteins and lipids within cilia and on the ciliary membrane are maintained to be distinct from those of the cytoplasm and plasma membrane, respectively, by the presence of the ciliary gate. INPP5E is a phosphoinositide 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety. In addition, the ciliary membrane localization of INPP5E is determined by the small GTPase ARL13B. However, it remained unclear as to how ARL13B participates in the localization of INPP5E. We here show that wild-type INPP5E, INPP5E(WT), in ARL13B-knockout cells and an INPP5E mutant defective in ARL13B binding, INPP5E(?CTS), in control cells were unable to show steady-state localization on the ciliary membrane. However, not only INPP5E(WT) but also INPP5E(?CTS) was able to rescue the abnormal localization of ciliary proteins in INPP5E-knockout cells. Analysis using the chemically induced dimerization system demonstrated that INPP5E(WT) in ARL13B-knockout cells and INPP5E(?CTS) in control cells were able to enter cilia, but neither was retained on the ciliary membrane due to the lack of the INPP5E-ARL13B interaction. Thus, our data demonstrate that binding of INPP5E to ARL13B is essential for its steady-state localization on the ciliary membrane but is dispensable for its entry into cilia.

SUBMITTER: Qiu H 

PROVIDER: S-EPMC7860134 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry.

Qiu Hantian H   Fujisawa Sayaka S   Nozaki Shohei S   Katoh Yohei Y   Nakayama Kazuhisa K  

Biology open 20210125 1


Compositions of proteins and lipids within cilia and on the ciliary membrane are maintained to be distinct from those of the cytoplasm and plasma membrane, respectively, by the presence of the ciliary gate. INPP5E is a phosphoinositide 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety. In addition, the ciliary membrane localization of INPP5E is determined by the small GTPase ARL13B. However, it remained unclear as to how ARL13B participates in  ...[more]

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