最新研究發(fā)現(xiàn),,一種之前了解較少的油脂在我們從干細(xì)胞發(fā)育成成熟個體的過程中起著重要的作用,。
Georgia醫(yī)學(xué)院的生物化學(xué)家Erhard Bieberich博士發(fā)現(xiàn),在胚胎發(fā)育的早期,,神經(jīng)酰胺幫助干細(xì)胞排列形成原始外胚層,這是胚胎組織形成的必要條件。大約90%的神經(jīng)酰胺結(jié)合在這些細(xì)胞的頂端,,幫助這些細(xì)胞排列。Bieberich表示:“細(xì)胞存在極性,,這是神經(jīng)酰胺最主要的作用,。細(xì)胞極性對于分化非常重要。”
事實上,,我們的生命開始于一個細(xì)胞團,,但在24小時內(nèi),一些細(xì)胞死去,,而另一些形成一個空心的細(xì)胞球,,這就是原始外胚層。接著這一結(jié)構(gòu)再分化為胚胎,。
結(jié)果發(fā)表在2月2日的《Journal of Biological Chemistry》上,,科學(xué)家發(fā)現(xiàn)細(xì)胞能形成神經(jīng)酰胺,它們在發(fā)育過程中起著很多作用,。它們幫助細(xì)胞膜形成,,還是神經(jīng)保護層的重要組成部分。
小組成員之一Guanghu Wang表示:“越來越多證據(jù)表明,神經(jīng)酰胺不只是結(jié)構(gòu)脂類,,而是一種幫助蛋白質(zhì)信息傳遞的信使,。”在2003年,Bieberich博士和他的同事報道了神經(jīng)酰胺和一種叫做PAR-4的蛋白合作,,能在大腦發(fā)育過程中排除不需要的細(xì)胞,。而現(xiàn)在,他的小組又證明了神經(jīng)酰胺在建立細(xì)胞極性過程中的作用,,通過和細(xì)胞的頂端結(jié)合,,就能觸發(fā)細(xì)胞之間的相互作用。
接下來,,小組還準(zhǔn)備繼續(xù)研究神經(jīng)酰胺在成熟細(xì)胞中起到的作用,,特別是在那些由于極性失去而癌化的細(xì)胞。 (譯自:physorg.com)
部分英文原文:
Ceramide Regulates Atypical PKC/-mediated Cell Polarity in Primitive Ectoderm Cells
A NOVEL FUNCTION OF SPHINGOLIPIDS IN MORPHOGENESIS*
Kannan Krishnamurthy1, Guanghu Wang1, Jeane Silva, Brian G. Condie, and Erhard Bieberich2
From the Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, Georgia 30912 and the ADepartment of Genetics, University of Georgia, Athens, Georgia 30602
In mammals, the primitive ectoderm is an epithelium of polarized cells that differentiates into all embryonic tissues. Our study shows that in primitive ectoderm cells, the sphingolipid ceramide was elevated and co-distributed with the small GTPase Cdc42 and cortical F-actin at the apicolateral cell membrane. Pharmacological or RNA interference-mediated inhibition of ceramide biosynthesis enhanced apoptosis and impaired primitive ectoderm formation in embryoid bodies differentiated from mouse embryonic stem cells. Primitive ectoderm formation was restored by incubation with ceramide or a ceramide analog. Ceramide depletion prevented plasma membrane translocation of PKC/, its interaction with Cdc42, and phosphorylation of GSK-3, a substrate of PKC/. Recombinant PKC formed a complex with the polarity protein Par6 and Cdc42 when bound to ceramide containing lipid vesicles. Our data suggest a novel mechanism by which a ceramide-induced, apicolateral polarity complex with PKC/ regulates primitive ectoderm cell polarity and morphogenesis.
更多英文原文鏈接:http://www.jbc.org/cgi/content/abstract/282/5/3379