最新研究发现,一种之前了解较少的油脂在我们从干细胞发育成成熟个体的过程中起着重要的作用。
Georgia医学院的生物化学家Erhard Bieberich博士发现,在胚胎发育的早期,神经酰胺帮助干细胞排列形成原始外胚层,这是胚胎组织形成的必要条件。大约90%的神经酰胺结合在这些细胞的顶端,帮助这些细胞排列。Bieberich表示:“细胞存在极性,这是神经酰胺最主要的作用。细胞极性对于分化非常重要。”
事实上,我们的生命开始于一个细胞团,但在24小时内,一些细胞死去,而另一些形成一个空心的细胞球,这就是原始外胚层。接着这一结构再分化为胚胎。
结果发表在2月2日的《Journal of Biological Chemistry》上,科学家发现细胞能形成神经酰胺,它们在发育过程中起着很多作用。它们帮助细胞膜形成,还是神经保护层的重要组成部分。
小组成员之一Guanghu Wang表示:“越来越多证据表明,神经酰胺不只是结构脂类,而是一种帮助蛋白质信息传递的信使。”在2003年,Bieberich博士和他的同事报道了神经酰胺和一种叫做PAR-4的蛋白合作,能在大脑发育过程中排除不需要的细胞。而现在,他的小组又证明了神经酰胺在建立细胞极性过程中的作用,通过和细胞的顶端结合,就能触发细胞之间的相互作用。
接下来,小组还准备继续研究神经酰胺在成熟细胞中起到的作用,特别是在那些由于极性失去而癌化的细胞。 (译自: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.
更多英文原文链接:http://www.jbc.org/cgi/content/abstract/282/5/3379