ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane

INPP5E, a phosphoinositide 5-phosphatase, localizes on the ciliary membrane via its C-terminal prenyl moiety, and maintains the distinct ciliary phosphoinositide composition. The ARL3 GTPase contributes to the ciliary membrane localization of INPP5E by stimulating the release of PDE6D bound to preny...

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Autores principales:	Sayaka Fujisawa, Hantian Qiu, Shohei Nozaki, Shuhei Chiba, Yohei Katoh, Kazuhisa Nakayama
Formato:	article
Lenguaje:	EN
Publicado:	The Company of Biologists 2021
Materias:	arl3 arl13b inpp5e cilia Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5dc95fdd7b6d4a12a441bc7369127e03
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spelling	oai:doaj.org-article:5dc95fdd7b6d4a12a441bc7369127e032021-11-28T16:01:23ZARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane2046-639010.1242/bio.058843https://doaj.org/article/5dc95fdd7b6d4a12a441bc7369127e032021-09-01T00:00:00Zhttp://bio.biologists.org/content/10/9/bio058843https://doaj.org/toc/2046-6390INPP5E, a phosphoinositide 5-phosphatase, localizes on the ciliary membrane via its C-terminal prenyl moiety, and maintains the distinct ciliary phosphoinositide composition. The ARL3 GTPase contributes to the ciliary membrane localization of INPP5E by stimulating the release of PDE6D bound to prenylated INPP5E. Another GTPase, ARL13B, which is localized on the ciliary membrane, contributes to the ciliary membrane retention of INPP5E by directly binding to its ciliary targeting sequence. However, as ARL13B was shown to act as a guanine nucleotide exchange factor (GEF) for ARL3, it is also possible that ARL13B indirectly mediates the ciliary INPP5E localization via activating ARL3. We here show that INPP5E is delocalized from cilia in both ARL3-knockout (KO) and ARL13B-KO cells. However, some of the abnormal phenotypes were different between these KO cells, while others were found to be common, indicating the parallel roles of ARL3 and ARL13B, at least concerning some cellular functions. For several variants of ARL13B, their ability to interact with INPP5E, rather than their ability as an ARL3-GEF, was associated with whether they could rescue the ciliary localization of INPP5E in ARL13B-KO cells. These observations together indicate that ARL13B determines the ciliary localization of INPP5E, mainly by its direct binding to INPP5E.Sayaka FujisawaHantian QiuShohei NozakiShuhei ChibaYohei KatohKazuhisa NakayamaThe Company of Biologistsarticlearl3arl13binpp5eciliaScienceQBiology (General)QH301-705.5ENBiology Open, Vol 10, Iss 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arl3 arl13b inpp5e cilia Science Q Biology (General) QH301-705.5
spellingShingle	arl3 arl13b inpp5e cilia Science Q Biology (General) QH301-705.5 Sayaka Fujisawa Hantian Qiu Shohei Nozaki Shuhei Chiba Yohei Katoh Kazuhisa Nakayama ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
description	INPP5E, a phosphoinositide 5-phosphatase, localizes on the ciliary membrane via its C-terminal prenyl moiety, and maintains the distinct ciliary phosphoinositide composition. The ARL3 GTPase contributes to the ciliary membrane localization of INPP5E by stimulating the release of PDE6D bound to prenylated INPP5E. Another GTPase, ARL13B, which is localized on the ciliary membrane, contributes to the ciliary membrane retention of INPP5E by directly binding to its ciliary targeting sequence. However, as ARL13B was shown to act as a guanine nucleotide exchange factor (GEF) for ARL3, it is also possible that ARL13B indirectly mediates the ciliary INPP5E localization via activating ARL3. We here show that INPP5E is delocalized from cilia in both ARL3-knockout (KO) and ARL13B-KO cells. However, some of the abnormal phenotypes were different between these KO cells, while others were found to be common, indicating the parallel roles of ARL3 and ARL13B, at least concerning some cellular functions. For several variants of ARL13B, their ability to interact with INPP5E, rather than their ability as an ARL3-GEF, was associated with whether they could rescue the ciliary localization of INPP5E in ARL13B-KO cells. These observations together indicate that ARL13B determines the ciliary localization of INPP5E, mainly by its direct binding to INPP5E.
format	article
author	Sayaka Fujisawa Hantian Qiu Shohei Nozaki Shuhei Chiba Yohei Katoh Kazuhisa Nakayama
author_facet	Sayaka Fujisawa Hantian Qiu Shohei Nozaki Shuhei Chiba Yohei Katoh Kazuhisa Nakayama
author_sort	Sayaka Fujisawa
title	ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
title_short	ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
title_full	ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
title_fullStr	ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
title_full_unstemmed	ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane
title_sort	arl3 and arl13b gtpases participate in distinct steps of inpp5e targeting to the ciliary membrane
publisher	The Company of Biologists
publishDate	2021
url	https://doaj.org/article/5dc95fdd7b6d4a12a441bc7369127e03
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ARL3 and ARL13B GTPases participate in distinct steps of INPP5E targeting to the ciliary membrane

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