Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1
Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1
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DOI：
10.1016/s0092-8674(01)00369-5
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发表时间：
2001-06-01
期刊：
影响因子：
64.5
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Lewis, PM;Dunn, MP;McMahon, AP
在脊椎动物的肢体区域中，来自极化活动后区（ZPA）的声刺猬（Shh）信号是前后极性的主要决定因素。通过将胆固醇共价连接至N-末端信号传导部分（N-Shh（p））的自动加工反应产生活性信号，从而将N-Shh（p）束缚至细胞膜。我们已经解决了这种亲脂性修饰在Shh介导的小鼠手指图案化中所起的作用。N-Shh（p）的分布和活性都表明N-Shh（p）直接作用于几百微米。相比之下，N-Shh，一种缺乏胆固醇的形式，保留了与N-Shh（p）相似的生物活性，但信号传导受到后部限制。因此，胆固醇修饰对于信号传导的正常范围是必需的。它似乎也是必要的适当调制信号的Shh受体，Ptc 1。
Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity (ZPA) is the primary determinant of anterior-posterior polarity in the vertebrate limb field. An active signal is produced by an autoprocessing reaction that covalently links cholesterol to the N-terminal signaling moiety (N-Shh(p)), tethering N-Shh(p) to the cell membrane. We have addressed the role played by this lipophilic modification in Shh-mediated patterning of mouse digits. Both the distribution and activity of N-Shh(p) indicate that N-Shh(p) acts directly over a few hundred microns. In contrast, N-Shh, a form that lacks cholesterol, retains similar biological activity to N-Shh(p), but signaling is posteriorly restricted. Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1.