Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis.

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis.
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DOI:
10.1242/jcs.136903
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发表时间:
2014-01-15
影响因子:
4
通讯作者:
Harada A
Harada A
中科院分区:
生物学2区
文献类型:
--
作者:
Sato T;Iwano T;Kunii M;Matsuda S;Mizuguchi R;Jung Y;Hagiwara H;Yoshihara Y;Yuzaki M;Harada R;Harada A

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已知小GTP结合蛋白Rab 8在细胞内转运和纤毛形成中起重要作用。我们以前已经证明,Rab 8a是需要本地化的顶端标记在各种生物体。Rab 8a有一个密切相关的同种型Rab 8b。为了确定Rab 8b是否可以补偿Rab 8a,我们产生Rab 8b敲除小鼠。虽然Rab 8b基因敲除小鼠没有表现出明显的表型,但Rab 8a和Rab 8b双基因敲除小鼠表现出顶端标记的错误定位,并且比Rab 8a基因敲除小鼠更早死亡。顶端标记物在双敲除小鼠中以三种细胞内模式积累。然而,双敲除小鼠的基底外侧和/或树突标记的定位似乎是正常的。各种初级和/或运动纤毛的形态和长度,以及纤毛细胞的频率似乎是相同的控制和双敲除小鼠。然而,在双敲除细胞中Rab 10的额外敲除大大降低了纤毛细胞的百分比。我们的研究结果突出了Rab 8a和Rab 8b在顶端运输中的补偿作用,以及顶端运输过程的复杂性。此外,Rab 8a和Rab 8b都不需要基底外侧和/或树突转运。然而,Rab 8a和Rab 8b的同时缺失对纤毛发生的影响很小,而Rab 10的额外缺失对纤毛发生的影响很大。
The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis.
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发表时间: 2008-04-01
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DOI: 10.1097/00001756-199206000-00017
发表时间: 1992-06-01
期刊: NEUROREPORT
影响因子: 1.7
作者:
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