生物谷報道： 日本群馬大學(xué)研究人員在新一期《自然》雜志網(wǎng)絡(luò)版上發(fā)表論文說，他們找到一種特定的蛋白質(zhì),，這種蛋白質(zhì)決定轉(zhuǎn)運(yùn)蛋白在小腸內(nèi)壁的分布狀況,，進(jìn)而影響細(xì)胞從小腸獲取營養(yǎng)。
群馬大學(xué)的研究人員報告說,，小腸內(nèi)壁集中分布著轉(zhuǎn)運(yùn)蛋白和酶,，這些轉(zhuǎn)運(yùn)蛋白負(fù)責(zé)將營養(yǎng)物質(zhì)從小腸運(yùn)入細(xì)胞，而決定轉(zhuǎn)運(yùn)蛋白在小腸內(nèi)壁分布狀況的物質(zhì)此前一直沒能被找到,。
此次日本研究人員在實(shí)驗(yàn)中首先確定了幾種候選物質(zhì),，在隨后的研究中，他們發(fā)現(xiàn)實(shí)驗(yàn)鼠如果缺失其中一種被其稱為“拉布８”的特定蛋白質(zhì),，它們就會患上營養(yǎng)失調(diào)癥,，并在出生３周至４周后死亡。
研究人員發(fā)現(xiàn),，缺失這種蛋白質(zhì)的實(shí)驗(yàn)鼠小腸內(nèi)的轉(zhuǎn)運(yùn)蛋白和酶停留在細(xì)胞內(nèi)部,，不能正常發(fā)揮作用，導(dǎo)致細(xì)胞幾乎無法獲取糖分和氨基酸,。研究人員認(rèn)為,，如果能對這種蛋白質(zhì)的機(jī)能實(shí)現(xiàn)人工調(diào)控，將有望幫助治療營養(yǎng)失調(diào)癥及肥胖癥,。（引自新華網(wǎng)）
原始出處:
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: [email protected]).
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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.
