哥本哈根大學(xué)的科學(xué)家開展在一項新的研究證實,,特定類型的碳水化合物在控制細(xì)胞生長的信號和神經(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)家在顯微鏡下運用一種特殊種類的果蠅開展研究。研究結(jié)果證實一中特定的碳水化合物組,,即所謂的糖脂,,其對細(xì)胞的復(fù)雜通信系統(tǒng)有影響。從長遠(yuǎn)來看,,這種模型的研究可以給神經(jīng)纖維瘤病患者帶來益處,。
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通路引起細(xì)胞生長的變化,。
糖脂存在于細(xì)胞膜上,發(fā)揮各種功能如保護細(xì)胞或被免疫系統(tǒng)識別,。在果蠅模型中,,我們阻止糖鏈的延長后,我們發(fā)現(xiàn)碳水化合物在控制正常細(xì)胞的生長中起著重要的作用,。當(dāng)糖鏈被縮短時,,組織生長,、細(xì)胞分裂顯著增加,。特別是糖鏈對中樞神經(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
PMC:
PMID:
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.