Lee J D, Kraus P, Gaiano N, Nery S, Kohtz J, Fishell G, Loomis C A, Treisman J E
Skirball Institute Developmental Genetics Program, Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Dev Biol. 2001 May 1;233(1):122-36. doi: 10.1006/dbio.2001.0218.
The Drosophila Hedgehog protein and its vertebrate counterpart Sonic hedgehog are required for a wide variety of patterning events throughout development. Hedgehog proteins are secreted from cells and undergo autocatalytic cleavage and cholesterol modification to produce a mature signaling domain. This domain of Sonic hedgehog has recently been shown to acquire an N-terminal acyl group in cell culture. We have investigated the in vivo role that such acylation might play in appendage patterning in mouse and Drosophila; in both species Hedgehog proteins define a posterior domain of the limb or wing. A mutant form of Sonic hedgehog that cannot undergo acylation retains significant ability to repattern the mouse limb. However, the corresponding mutation in Drosophila Hedgehog renders it inactive in vivo, although it is normally processed. Furthermore, overexpression of the mutant form has dominant negative effects on Hedgehog signaling. These data suggest that the importance of the N-terminal cysteine of mature Hedgehog in patterning appendages differs between species.
果蝇的刺猬蛋白及其脊椎动物对应物音猬因子在整个发育过程中的多种模式形成事件中是必需的。刺猬蛋白从细胞中分泌出来，经过自催化切割和胆固醇修饰以产生成熟的信号结构域。最近在细胞培养中已表明，音猬因子的这个结构域会获得一个N端酰基。我们研究了这种酰化作用在小鼠和果蝇附肢模式形成中可能发挥的体内作用；在这两个物种中，刺猬蛋白都定义了肢体或翅膀的后部区域。一种不能进行酰化的音猬因子突变形式仍保留了显著的重新塑造小鼠肢体的能力。然而，果蝇刺猬蛋白中的相应突变使其在体内失去活性，尽管它通常会被加工。此外，突变形式的过表达对刺猬信号通路有显性负效应。这些数据表明，成熟刺猬蛋白的N端半胱氨酸在附肢模式形成中的重要性在不同物种之间存在差异。
