期刊
BIOLOGY OPEN
卷 4, 期 1, 页码 86-94出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.20148532
关键词
Rab11a; Knockout mouse; Cell polarity; Brain; Intestine; Apical membrane
类别
资金
- Japanese Society for the Promotion of Science (KAKENHI) [24390046]
- Mitsubishi Foundation and Takeda Science Foundation
- Grants-in-Aid for Scientific Research [25460269, 24390046, 25860141] Funding Source: KAKEN
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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