
研究发现一种脂质在胚胎发育中起重要作用
最新研究发现,一种之前了解较少的脂质,在干细胞发育为成熟个体的过程中,发挥重要的功能。
乔治亚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%的神经酰胺结合于这些细胞的顶端,帮助这些细胞排列。Bieberich表示,细胞存在着极性是神经酰胺最主要的功能,细胞极性对于分化非常重要。
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。
这项结果发表于2月2日的Journal of Biological Chemistry中,科学家发现细胞能形成神经酰胺,它们在发育过程中相当重要,可以帮助细胞膜形成,同时也是神经保护层的重要组成分。
小组成员之一Guanghu Wang表示,越来越多证据显示,神经酰胺不只是结构脂质,也是一种帮助蛋白质信息传递的讯息分子。
Bieberich博士于2003年发表的研究指出,神经酰胺和一种名为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,他的研究小组又证明了神经酰胺在建立细胞极性过程中扮演的角色。
研究小组接着将继续研究神经酰胺在成熟细胞中发挥的功能,特别是在那些因为失去极性而癌化的细胞。
(资料来源 : Bio.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 Krishnamurthy
1, Guanghu Wang
1, Jeane Silva
, Brian G. Condie
, and Erhard Bieberich
2
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.
原文出处:J. Biol. Chem., Feb 2007; 282: 3379 - 3390 ; doi:10.1074/jbc.M607779200
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