GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
- Ulsan National Institute of Science and Technology, Republic of Korea
- Institute for Basic Science, Republic of Korea
- Kyungpook National University, Republic of Korea
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript, supporting file and source data files
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GJA1 IP/MS datasetDryad Digital Repository, doi:10.5061/dryad.tht76hdxt.
Article and author information
Author details
Funding
Korea National Research Foundation (2021R1A2B5B02002285)
- Tae Joo Park
Institute for Basic Science (IBS-R001-D1)
- Taejoon Kwon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gregory J Pazour, University of Massachusetts Medical School, United States
Ethics
Animal experimentation: All animal experiments were performed with appropriate ethical approval from the UNIST Institutional Animal Care and Use Committee (UNISTIACUC-19-22, UNISTIACUC-20-26).
Version history
- Preprint posted: November 16, 2020 (view preprint)
- Received: June 13, 2022
- Accepted: August 11, 2022
- Accepted Manuscript published: August 25, 2022 (version 1)
- Version of Record published: September 6, 2022 (version 2)
Copyright
© 2022, Jang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base
eLife 11:e81016.
https://doi.org/10.7554/eLife.81016
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