An acylatable residue of hedgehog is differentially required in Drosophila and mouse limb development
An acylatable residue of hedgehog is differentially required in Drosophila and mouse limb development
复制标题
DOI：
10.1006/dbio.2001.0218
复制
发表时间：
2001-05-01
影响因子：
2.7
通讯作者：
Treisman, JE
中科院分区：
文献类型：
--
作者：
Lee, JD;Kraus, P;Treisman, JE
果蝇 Hedgehog 蛋白及其脊椎动物对应物 Sonic hedgehog 是整个发育过程中各种模式事件所必需的。 Hedgehog 蛋白从细胞中分泌出来，经过自催化裂解和胆固醇修饰，产生成熟的信号传导结构域。最近，Sonic Hedgehog 的这个结构域已被证明在细胞培养物中获得了 N 末端酰基。我们研究了这种酰化在小鼠和果蝇的附属物图案形成中可能发挥的体内作用；在这两个物种中，刺猬蛋白定义了肢体或翅膀的后部区域。无法进行酰化的音速刺猬的突变形式保留了重新塑造小鼠肢体的显着能力。然而，果蝇刺猬中的相应突变使其在体内失去活性，尽管它是正常加工的。此外，突变体形式的过度表达对 Hedgehog 信号传导具有显着的负面影响。这些数据表明，成熟刺猬的 N 末端半胱氨酸在附属物图案中的重要性因物种而异。 (C) 2001 年学术出版社。
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. (C) 2001 Academic Press.