Cargando…

GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base

The gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein α1 (GJA1) is the most commonly expressed subunit. A recent study showed that GJA1 is necessary for the maintenance of motile cilia; however, the molecular mechanism and fu...

Descripción completa

Detalles Bibliográficos
Autores principales: Jang, Dong Gil, Kwon, Keun Yeong, Kweon, Yeong Cheon, Kim, Byung-gyu, Myung, Kyungjae, Lee, Hyun-Shik, Young Park, Chan, Kwon, Taejoon, Park, Tae Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448326/
https://www.ncbi.nlm.nih.gov/pubmed/36004726
http://dx.doi.org/10.7554/eLife.81016
_version_ 1784784038711525376
author Jang, Dong Gil
Kwon, Keun Yeong
Kweon, Yeong Cheon
Kim, Byung-gyu
Myung, Kyungjae
Lee, Hyun-Shik
Young Park, Chan
Kwon, Taejoon
Park, Tae Joo
author_facet Jang, Dong Gil
Kwon, Keun Yeong
Kweon, Yeong Cheon
Kim, Byung-gyu
Myung, Kyungjae
Lee, Hyun-Shik
Young Park, Chan
Kwon, Taejoon
Park, Tae Joo
author_sort Jang, Dong Gil
collection PubMed
description The gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein α1 (GJA1) is the most commonly expressed subunit. A recent study showed that GJA1 is necessary for the maintenance of motile cilia; however, the molecular mechanism and function of GJA1 in ciliogenesis remain unknown. Here, we examined the functions of GJA1 during ciliogenesis in human retinal pigment epithelium-1 and Xenopus laevis embryonic multiciliated-cells. GJA1 localizes to the motile ciliary axonemes or pericentriolar regions beneath the primary cilium. GJA1 depletion caused malformation of both the primary cilium and motile cilia. Further study revealed that GJA1 depletion affected several ciliary proteins such as BBS4, CP110, and Rab11 in the pericentriolar region and basal body. Interestingly, CP110 removal from the mother centriole was significantly reduced by GJA1 depletion. Importantly, Rab11, a key regulator during ciliogenesis, was immunoprecipitated with GJA1 and GJA1 knockdown caused the mislocalization of Rab11. These findings suggest that GJA1 regulates ciliogenesis by interacting with the Rab11-Rab8 ciliary trafficking pathway.
format Online
Article
Text
id pubmed-9448326
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-94483262022-09-07 GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base Jang, Dong Gil Kwon, Keun Yeong Kweon, Yeong Cheon Kim, Byung-gyu Myung, Kyungjae Lee, Hyun-Shik Young Park, Chan Kwon, Taejoon Park, Tae Joo eLife Cell Biology The gap junction complex functions as a transport channel across the membrane. Among gap junction subunits, gap junction protein α1 (GJA1) is the most commonly expressed subunit. A recent study showed that GJA1 is necessary for the maintenance of motile cilia; however, the molecular mechanism and function of GJA1 in ciliogenesis remain unknown. Here, we examined the functions of GJA1 during ciliogenesis in human retinal pigment epithelium-1 and Xenopus laevis embryonic multiciliated-cells. GJA1 localizes to the motile ciliary axonemes or pericentriolar regions beneath the primary cilium. GJA1 depletion caused malformation of both the primary cilium and motile cilia. Further study revealed that GJA1 depletion affected several ciliary proteins such as BBS4, CP110, and Rab11 in the pericentriolar region and basal body. Interestingly, CP110 removal from the mother centriole was significantly reduced by GJA1 depletion. Importantly, Rab11, a key regulator during ciliogenesis, was immunoprecipitated with GJA1 and GJA1 knockdown caused the mislocalization of Rab11. These findings suggest that GJA1 regulates ciliogenesis by interacting with the Rab11-Rab8 ciliary trafficking pathway. eLife Sciences Publications, Ltd 2022-08-25 /pmc/articles/PMC9448326/ /pubmed/36004726 http://dx.doi.org/10.7554/eLife.81016 Text en © 2022, Jang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Jang, Dong Gil
Kwon, Keun Yeong
Kweon, Yeong Cheon
Kim, Byung-gyu
Myung, Kyungjae
Lee, Hyun-Shik
Young Park, Chan
Kwon, Taejoon
Park, Tae Joo
GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title_full GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title_fullStr GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title_full_unstemmed GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title_short GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
title_sort gja1 depletion causes ciliary defects by affecting rab11 trafficking to the ciliary base
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448326/
https://www.ncbi.nlm.nih.gov/pubmed/36004726
http://dx.doi.org/10.7554/eLife.81016
work_keys_str_mv AT jangdonggil gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT kwonkeunyeong gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT kweonyeongcheon gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT kimbyunggyu gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT myungkyungjae gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT leehyunshik gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT youngparkchan gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT kwontaejoon gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase
AT parktaejoo gja1depletioncausesciliarydefectsbyaffectingrab11traffickingtotheciliarybase