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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/81016 |
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| author | Dong Gil Jang Keun Yeong Kwon Yeong Cheon Kweon Byung-gyu Kim Kyungjae Myung Hyun-Shik Lee Chan Young Park Taejoon Kwon Tae Joo Park |
| author_facet | Dong Gil Jang Keun Yeong Kwon Yeong Cheon Kweon Byung-gyu Kim Kyungjae Myung Hyun-Shik Lee Chan Young Park Taejoon Kwon Tae Joo Park |
| author_sort | Dong Gil Jang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:34:07Z |
| format | Article |
| id | doaj.art-b10320ea19874a318706403064d7951a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:34:07Z |
| publishDate | 2022-08-01 |
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| series | eLife |
| spelling | doaj.art-b10320ea19874a318706403064d7951a2022-12-22T03:25:03ZengeLife Sciences Publications LtdeLife2050-084X2022-08-011110.7554/eLife.81016GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary baseDong Gil Jang0Keun Yeong Kwon1Yeong Cheon Kweon2Byung-gyu Kim3Kyungjae Myung4Hyun-Shik Lee5Chan Young Park6Taejoon Kwon7https://orcid.org/0000-0002-9794-6112Tae Joo Park8https://orcid.org/0000-0003-3176-177XDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of KoreaDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of KoreaDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of KoreaCenter for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of KoreaCenter for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of KoreaKNU-Center for Nonlinear Dynamics, CMRI, School of Life Sciences, BK21 Plus KNU Creative Bio Research Group, College of Natural Sciences, Kyungpook National University, Daegu, Republic of KoreaDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of KoreaCenter for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of Korea; Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of KoreaDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea; Center for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of KoreaThe 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.https://elifesciences.org/articles/81016ciliaGJA1Rab11 |
| spellingShingle | Dong Gil Jang Keun Yeong Kwon Yeong Cheon Kweon Byung-gyu Kim Kyungjae Myung Hyun-Shik Lee Chan Young Park Taejoon Kwon Tae Joo Park GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base eLife cilia GJA1 Rab11 |
| 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 | cilia GJA1 Rab11 |
| url | https://elifesciences.org/articles/81016 |
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