Phylogenetic profiling and cellular analyses of ARL16 reveal roles in traffic of IFT140 and INPP5E.
Phylogenetic profiling and cellular analyses of ARL16 reveal roles in traffic of IFT140 and INPP5E.
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DOI：
10.1091/mbc.e21-10-0509-t
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发表时间：
2022-04-01
影响因子：
3.3
通讯作者：
Kahn, Richard A.
中科院分区：
文献类型：
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作者：
Dewees, Skylar, I;Vargova, Romana;Hardin, Katherine R.;Turn, Rachel E.;Devi, Saroja;Linnert, Joshua;Wolfrum, Uwe;Caspary, Tamara;Elias, Marek;Kahn, Richard A.
ARF调节GTP酶家族由来已久，据预测在最后一个真核共同祖先中存在16个成员。我们对不同物种中的类似物进行了系统发育分析，发现了四个与纤毛/鞭毛相关的家族成员：ARL3、ARL6、ARL13和ARL16。此前没有证据表明ARL16与纤毛或其他细胞功能有关，尽管它存在于真核生物中。小鼠胚胎成纤维细胞(MEF)中ARL16的缺失导致纤毛生成减少，但纤毛长度增加。我们还在MEF中发现了Arl16基因敲除(KO)来改变纤毛蛋白的含量，包括Ar13b、ARL3、INPP5E和IFT-A核心成分IFT140的丢失。相反，INPP5E和IFT140都在Arl16 KO系的高尔基体积累，而其他鞭毛内转运(IFT)蛋白不积累，这表明从高尔基体到纤毛的运输存在特定缺陷。我们认为ARL16调节高尔基体-纤毛的运输途径，并且在高尔基体的IFT140和INPP5E的出口中是特别需要的。
The ARF family of regulatory GTPases is ancient, with 16 members predicted to have been present in the last eukaryotic common ancestor. Our phylogenetic profiling of paralogues in diverse species identified four family members whose presence correlates with that of a cilium/flagellum: ARL3, ARL6, ARL13, and ARL16. No prior evidence links ARL16 to cilia or other cell functions, despite its presence throughout eukaryotes. Deletion of ARL16 in mouse embryonic fibroblasts (MEFs) results in decreased ciliogenesis yet increased ciliary length. We also found Arl16 knockout (KO) in MEFs to alter ciliary protein content, including loss of ARL13B, ARL3, INPP5E, and the IFT-A core component IFT140. Instead, both INPP5E and IFT140 accumulate at the Golgi in Arl16 KO lines, while other intraflagellar transport (IFT) proteins do not, suggesting a specific defect in traffic from Golgi to cilia. We propose that ARL16 regulates a Golgi–cilia traffic pathway and is required specifically in the export of IFT140 and INPP5E from the Golgi.