Rab GTPases are required for early orientation of the left-right axis in Xenopus.
Rab GTPases are required for early orientation of the left-right axis in Xenopus.
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DOI：
10.1016/j.mod.2012.11.007
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发表时间：
2013-04
影响因子：
2.6
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Vandenberg LN;Morrie RD;Seebohm G;Lemire JM;Levin M
非洲爪蟾胚胎中左右（LR）模式化的最早步骤是由偏置的细胞内转运驱动的，这确保了母体离子通道和泵在前2-4个卵裂球中的一致不对称定位。随后，这些转运蛋白的离子差异净流出产生生物电不对称性;这种LR电压梯度使小信号分子沿着LR轴重新分布，这些小信号分子随后调节正常左侧Nodal的转录。因此，该系统将单细胞手性放大为跨多细胞场的真正左右不对称性。使用分子遗传获得和功能丧失试剂的研究已经表征了非洲爪蟾这种早期途径中所涉及的许多步骤。然而，一个关键的问题仍然存在：如何解释手性细胞骨架结构定位于左侧或右侧的离子转运？由于Rab GTP酶几乎调节膜运输的所有方面，我们假设一个或多个Rab蛋白负责母体离子通道或泵蛋白的定向、不对称穿梭。在使用显性阴性和野生型（过表达）mRNA对四种不同的Rabs进行筛选后，我们发现Rab 11表达的改变使不对称基因表达和器官部位随机化。我们还表明，两个离子转运蛋白亚基的不对称定位需要Rab 11的功能，Rab 11与这些亚基中的至少一个密切相关。然而，重要的是，我们发现内源性Rab 11 mRNA和蛋白质在早期胚胎中对称表达。我们的结论是Rab 11介导的运输是负责早期卵裂球内的货物的运动，Rab 11的表达需要在整个早期胚胎的适当LR图案。
The earliest steps of left–right (LR) patterning in Xenopus embryos are driven by biased intracellular transport that ensures a consistently asymmetric localization of maternal ion channels and pumps in the first 2–4 blastomeres. The subsequent differential net efflux of ions by these transporters generates a bioelectrical asymmetry; this LR voltage gradient redistributes small signaling molecules along the LR axis that later regulate transcription of the normally left-sided Nodal. This system thus amplifies single cell chirality into a true left–right asymmetry across multi-cellular fields. Studies using molecular-genetic gain- and loss-of-function reagents have characterized many of the steps involved in this early pathway in Xenopus. Yet one key question remains: how is the chiral cytoskeletal architecture interpreted to localize ion transporters to the left or right side? Because Rab GTPases regulate nearly all aspects of membrane trafficking, we hypothesized that one or more Rab proteins were responsible for the directed, asymmetric shuttling of maternal ion channel or pump proteins. After performing a screen using dominant negative and wildtype (overexpressing) mRNAs for four different Rabs, we found that alterations in Rab11 expression randomize both asymmetric gene expression and organ situs. We also demonstrated that the asymmetric localization of two ion transporter subunits requires Rab11 function, and that Rab11 is closely associated with at least one of these subunits. Yet, importantly, we found that endogenous Rab11 mRNA and protein are expressed symmetrically in the early embryo. We conclude that Rab11-mediated transport is responsible for the movement of cargo within early blastomeres, and that Rab11 expression is required throughout the early embryo for proper LR patterning.
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影响因子：
5.4
作者：
Eisfeld, Amie J.;Kawakami, Eiryo;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
3.7
作者：
Antic D;Stubbs JL;Suyama K;Kintner C;Scott MP;Axelrod JD
通讯作者：
Axelrod JD
影响因子：
21.3
作者：
Borovina, Antonia;Superina, Simone;Ciruna, Brian
通讯作者：
Ciruna, Brian
DOI：
10.1111/j.1749-6632.1977.tb41927.x
发表时间：
1977-09-30
影响因子：
5.2
作者：
Dawson, J L
通讯作者：
Dawson, J L
DOI：
10.1038/nsb803
发表时间：
2002-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Ali, MY;Uemura, S;Ishiwata, S
通讯作者：
Ishiwata, S