哥本哈根大學(xué)的科學(xué)家開(kāi)展在一項(xiàng)新的研究證實(shí),，特定類(lèi)型的碳水化合物在控制細(xì)胞生長(zhǎng)的信號(hào)和神經(jīng)系統(tǒng)的發(fā)育中起著重要的作用,。特別是這碳水化合物的缺陷可能導(dǎo)致細(xì)胞生長(zhǎng)失控為特征的神經(jīng)纖維瘤病遺傳性疾病以及其它某些類(lèi)型的癌癥。相關(guān)研究論文發(fā)表在PNAS期刊上,。
哥本哈根大學(xué)衛(wèi)生和醫(yī)學(xué)科學(xué)學(xué)院在的科學(xué)家在顯微鏡下運(yùn)用一種特殊種類(lèi)的果蠅開(kāi)展研究,。研究結(jié)果證實(shí)一中特定的碳水化合物組，即所謂的糖脂,，其對(duì)細(xì)胞的復(fù)雜通信系統(tǒng)有影響,。從長(zhǎng)遠(yuǎn)來(lái)看，這種模型的研究可以給神經(jīng)纖維瘤病患者帶來(lái)益處,。
醫(yī)生在神經(jīng)科學(xué)和藥理學(xué)教授Ole Kjærulff等表示：現(xiàn)在,，我們發(fā)現(xiàn)最重要的事情是碳水化合物在細(xì)胞之間的溝通交流中有新功能。我們還揭示了如何干擾給信號(hào)通路引起細(xì)胞生長(zhǎng)的變化,。
糖脂存在于細(xì)胞膜上,，發(fā)揮各種功能如保護(hù)細(xì)胞或被免疫系統(tǒng)識(shí)別。在果蠅模型中,，我們阻止糖鏈的延長(zhǎng)后,，我們發(fā)現(xiàn)碳水化合物在控制正常細(xì)胞的生長(zhǎng)中起著重要的作用。當(dāng)糖鏈被縮短時(shí),，組織生長(zhǎng)、細(xì)胞分裂顯著增加,。特別是糖鏈對(duì)中樞神經(jīng)系統(tǒng)的神經(jīng)膠質(zhì)細(xì)胞的影響最明顯,。（生物谷：Bioon.com）
doi:10.1073/pnas.1115453109
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Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension
Katja Dahlgaarda, Anita Jungb, Klaus Qvortrupc, Henrik Clausena, Ole Kjaerulffb, and Hans H. Wandalla
Glycosphingolipids (GSLs) are of fundamental importance in the nervous system. However, the molecular details associated with GSL function are largely unknown, in part because of the complexity of GSL biosynthesis in vertebrates. In Drosophila, only one major GSL biosynthetic pathway exists, controlled by the glycosyltransferase Egghead (Egh). Here we discovered that loss of Egh causes overgrowth of peripheral nerves and attraction of immune cells to the nerves. This phenotype is reminiscent of the human disorder neurofibromatosis type 1, which is characterized by disfiguring nerve sheath tumors with mast cell infiltration, increased cancer risk, and learning deficits. Neurofibromatosis type 1 is due to a reduction of the tumor suppressor neurofibromin, a negative regulator of the small GTPase Ras. Enhanced Ras signaling promotes glial growth through activation of phosphatidylinositol 3-kinase (PI3K) and its downstream kinase Akt. We find that overgrowth of peripheral nerves in egh mutants is suppressed by down-regulation of the PI3K signaling pathway by expression of either dominant-negative PI3K, the tumor suppressor PTEN, or the transcription factor FOXO in the subperineurial glia. These results show that loss of the glycosyltransferase Egh affects membrane signaling and activation of PI3K signaling in glia of the peripheral nervous system, and suggest that glycosyltransferases may suppress proliferation.
