Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids
Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids
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DOI：
10.1242/dev.01301
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发表时间：
2004-09-01
期刊：
影响因子：
4.6
通讯作者：
Kohtz, JD
中科院分区：
文献类型：
--
作者：
Feng, J;White, B;Kohtz, JD
Shh蛋白含有N-末端和C-末端脂质。这些脂质部分的功能冗余目前尚不清楚。在这里，我们比较了N-和C-末端脂质在早期大鼠纹状体神经元分化，膜协会和多聚化，并在斑马鱼前脑的ventralizing活动的相对作用。我们表明，这些脂质协同作用，在细胞拴系和形成一个大的（L）多聚体（669 kDa）。然而，C-末端脂质拮抗大鼠纹状体神经元分化诱导活性的N-末端脂质。此外，多聚化是必需的，但不足以诱导分化活性。基于不同的N-和C-脂质含有Shh蛋白在大鼠胚胎中的存在，并在其不同的活动，我们建议，N-和C-末端的脂质都需要参与远程信号的多聚体的形成，和C-末端的脂质可以通过减少Shh活性，直到它达到其远程目标在远程信号。比较分析的ventralizing活动的不同的N-和C-末端含脂质的Shh蛋白质在斑马鱼前脑显示，至少一种脂质的存在下，需要的信号传导活动，这表明脂质修饰的Shh是一个保守的要求，在前脑的啮齿动物和斑马鱼的信号。
The Shh protein contains both N-terminal and C-terminal lipids. The functional redundancy of these lipid moieties is presently unclear. Here, we compare the relative roles of the N- and C-terminal lipids in early rat striatal neuronal differentiation, membrane association and multimerization, and ventralizing activity in the zebrafish forebrain. We show that these lipid act synergistically in cell tethering and the formation of a large (L) multimer (669 kDa). However, the C-terminal lipid antagonizes the rat striatal neuronal differentiation-inducing activity of the N-terminal lipid. In addition, multimerization is required but not sufficient for the differentiation-inducing activity. Based on the presence of different N- and C-lipid-containing Shh proteins in the rat embryo, and on their different activities, we propose that both N- and C-terminal lipids are required for the formation of multimers involved in long-range signaling, and that the C-terminal lipid may function in long-range signaling by reducing Shh activity until it reaches its long-range target. Comparative analysis of the ventralizing activities of different N- and C-terminal lipid-containing Shh proteins in the zebrafish forebrain shows that the presence of at least one lipid is required for signaling activity, suggesting that lipid modification of Shh is a conserved requirement for signaling in the forebrain of rodents and zebrafish.