生物谷报道： 日本群马大学研究人员在新一期《自然》杂志网络版上发表论文说，他们找到一种特定的蛋白质，这种蛋白质决定转运蛋白在小肠内壁的分布状况，进而影响细胞从小肠获取营养。
群马大学的研究人员报告说，小肠内壁集中分布着转运蛋白和酶，这些转运蛋白负责将营养物质从小肠运入细胞，而决定转运蛋白在小肠内壁分布状况的物质此前一直没能被找到。
此次日本研究人员在实验中首先确定了几种候选物质，在随后的研究中，他们发现实验鼠如果缺失其中一种被其称为“拉布８”的特定蛋白质，它们就会患上营养失调症，并在出生３周至４周后死亡。
研究人员发现，缺失这种蛋白质的实验鼠小肠内的转运蛋白和酶停留在细胞内部，不能正常发挥作用，导致细胞几乎无法获取糖分和氨基酸。研究人员认为，如果能对这种蛋白质的机能实现人工调控，将有望帮助治疗营养失调症及肥胖症。（引自新华网）
原始出处:
Nature advance online publication 27 June 2007 | doi:10.1038/nature05929; Received 15 April 2007; Accepted 15 May 2007; Published online 27 June 2007
The Rab8 GTPase regulates apical protein localization in intestinal cells
Takashi Sato1, Sotaro Mushiake2, Yukio Kato3, Ken Sato1, Miyuki Sato1, Naoki Takeda4, Keiichi Ozono2, Kazunori Miki5, Yoshiyuki Kubo3, Akira Tsuji3, Reiko Harada1 & Akihiro Harada1
Laboratory of Molecular Traffic, Department of Molecular and Cellullar Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan
Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan
Division of Transgenic Technology, Center for Animal Resources and Development (CARD), IRDA, Kumamoto University, Kumamoto 860-0811, Japan
Department of Pediatrics, Itami Municipal Hospital, Hyogo 664-8540, Japan
Correspondence to: Akihiro Harada1 Correspondence and requests for materials should be addressed to A.H. (Email: aharada@showa.gunma-u.ac.jp).
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A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells1, 2, 3, 4, 5, 6, 7. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway8, 9. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine.
