Rab11a is required for apical protein localisation in the intestine.
Rab11a is required for apical protein localisation in the intestine.
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DOI：
10.1242/bio.20148532
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发表时间：
2014-12-19
期刊：
影响因子：
2.4
通讯作者：
Harada A
中科院分区：
文献类型：
--
作者：
Sobajima T;Yoshimura S;Iwano T;Kunii M;Watanabe M;Atik N;Mushiake S;Morii E;Koyama Y;Miyoshi E;Harada A
小GTTRab11在蛋白质向质膜的再循环以及上皮细胞和神经元中的极化运输中起重要作用。我们产生了Rab11a缺陷的条件性敲除小鼠。Rab11a缺陷小鼠是胚胎致死的，脑特异性Rab11a敲除小鼠的脑结构没有明显的异常。相比之下，马槟榔特异性Rab11a基因敲除小鼠在出生后约1周开始死亡。基因敲除小鼠肠道中的顶端蛋白质在细胞质中积累并错误定位于基底外侧质膜，而基底外侧蛋白质的定位不受影响。在基因敲除小鼠中还观察到较短的微绒毛和微绒毛包涵体。还观察到血清饥饿标记物的升高，可能是由顶端蛋白质的错误定位和营养摄取减少引起的。此外，Rab8a在Rab11a敲除小鼠中是错误定位的。相反，Rab11a在Rab8a基因敲除小鼠和肌球蛋白Vb基因突变的微绒毛萎缩患者中定位错误。我们的数据显示Rab11a在肠道顶端蛋白定位中的重要作用，并证明Rab11a，Rab8a和肌球蛋白Vb在体内的功能关系。
The small GTPase Rab11 plays an important role in the recycling of proteins to the plasma membrane as well as in polarised transport in epithelial cells and neurons. We generated conditional knockout mice deficient in Rab11a. Rab11a-deficient mice are embryonic lethal, and brain-specific Rab11a knockout mice show no overt abnormalities in brain architecture. In contrast, intestine-specific Rab11a knockout mice begin dying approximately 1 week after birth. Apical proteins in the intestines of knockout mice accumulate in the cytoplasm and mislocalise to the basolateral plasma membrane, whereas the localisation of basolateral proteins is unaffected. Shorter microvilli and microvillus inclusion bodies are also observed in the knockout mice. Elevation of a serum starvation marker was also observed, likely caused by the mislocalisation of apical proteins and reduced nutrient uptake. In addition, Rab8a is mislocalised in Rab11a knockout mice. Conversely, Rab11a is mislocalised in Rab8a knockout mice and in a microvillus atrophy patient, which has a mutation in the myosin Vb gene. Our data show an essential role for Rab11a in the localisation of apical proteins in the intestine and demonstrate functional relationships between Rab11a, Rab8a and myosin Vb in vivo.
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