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Elife 2022 Aug 25;11. doi: 10.7554/eLife.81016.
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GJA1 depletion causes ciliary defects by affecting Rab11 trafficking to the ciliary base.

Jang DG , Kwon KY , Kweon YC , Kim BG , Myung K , Lee HS , Young Park C , Kwon T , Park TJ .

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.

PubMed ID: 36004726
PMC ID: PMC9448326
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: arl13b ccp110 dnah9 gja1 ift20 ift88 nodal pitx2 rab11a rab8a ttbk2
GO keywords: gap junction
Antibodies: Cp110 Ab1 HA Ab2 Myh6 Ab1 RFP Ab3 Tuba4b Ab4
Morpholinos: gja1 MO1

Article Images: [+] show captions
References [+] :
Aasen, Connexins: junctional and non-junctional modulators of proliferation. 2015, Pubmed