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ARL3 GTPases 促进了动纤毛中 ODA16 从 IFT 上的卸载。

ARL3 GTPases facilitate ODA16 unloading from IFT in motile cilia.

机构信息

Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Sci Adv. 2024 Sep 6;10(36):eadq2950. doi: 10.1126/sciadv.adq2950. Epub 2024 Sep 4.

DOI:10.1126/sciadv.adq2950
PMID:39231220
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11373600/
Abstract

Eukaryotic cilia and flagella are essential for cell motility and sensory functions. Their biogenesis and maintenance rely on the intraflagellar transport (IFT). Several cargo adapters have been identified to aid IFT cargo transport, but how ciliary cargos are discharged from the IFT remains largely unknown. During our explorations of small GTPases ARL13 and ARL3 in , we found that ODA16, a known IFT cargo adapter present exclusively in motile cilia, is a specific effector of ARL3. In the cilia, active ARL3 GTPases bind to ODA16 and dissociate ODA16 from the IFT complex. Depletion of ARL3 GTPases stabilizes ODA16 interaction with the IFT, leading to ODA16 accumulation in cilia and defects in axonemal assembly. The interactions between human ODA16 homolog HsDAW1 and ARL GTPases are conserved, and these interactions are altered in HsDAW1 disease variants. These findings revealed a conserved function of ARL GTPases in IFT transport of motile ciliary components, and a mechanism of cargo unloading from the IFT.

摘要

真核细胞纤毛和鞭毛对于细胞运动和感觉功能至关重要。它们的发生和维持依赖于鞭毛内运输（IFT）。已经鉴定出几种货物衔接器来辅助 IFT 货物运输，但 IFT 如何从纤毛中排出货物仍知之甚少。在探索小 GTPase ARL13 和 ARL3 的过程中，我们发现 ODA16，一种仅存在于运动纤毛中的已知 IFT 货物衔接器，是 ARL3 的特异性效应物。在纤毛中，活性 ARL3 GTPases 与 ODA16 结合并将 ODA16 从 IFT 复合物中解离。ARL3 GTPases 的耗竭稳定了 ODA16 与 IFT 的相互作用，导致 ODA16 在纤毛中积累和轴丝组装缺陷。人源 ODA16 同源物 HsDAW1 与 ARL GTPases 之间的相互作用是保守的，并且这些相互作用在 HsDAW1 疾病变体中发生改变。这些发现揭示了 ARL GTPases 在 IFT 运输运动性纤毛成分中的保守功能，以及货物从 IFT 中卸载的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/5faeb888710c/sciadv.adq2950-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/f73da17d2f9b/sciadv.adq2950-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/61e3c9054407/sciadv.adq2950-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/938605c1f673/sciadv.adq2950-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/96e7fee5e9cd/sciadv.adq2950-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/01e42bdd6959/sciadv.adq2950-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/5faeb888710c/sciadv.adq2950-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/f73da17d2f9b/sciadv.adq2950-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/7acced248e38/sciadv.adq2950-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/61e3c9054407/sciadv.adq2950-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/938605c1f673/sciadv.adq2950-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/96e7fee5e9cd/sciadv.adq2950-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/01e42bdd6959/sciadv.adq2950-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11373600/5faeb888710c/sciadv.adq2950-f7.jpg

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