Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signalling.
Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signalling.
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DOI：
10.1038/ncomms5849
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发表时间：
2014-09-12
影响因子：
16.6
通讯作者：
Roelink, Henk
中科院分区：
文献类型：
--
作者：
Kwong, Lina;Bijlsma, Maarten F.;Roelink, Henk
Sonic Hedgehog（Shh）的分布是一个高度调节和关键的发育过程。有几种负反馈机制，包括Shh诱导的Hedgehog相互作用蛋白（Hhip）上调。Hip螯合Shh，导致非细胞自主抑制该途径。Hhip过度表达对神经管发育有严重影响，这就提出了一个问题，为什么正常的Hhip表达位点对Shh的反应似乎没有受损。在这里，我们表明，虽然Hip能够离开其合成位点，自主抑制Shh非细胞，但Smoothened（Smo）的激活会显著增加Hip的内化和自主降解细胞。虽然Hip不能自主地抑制Smo激活的后果，但它可以自主地抑制Shh反应。我们的数据提供了一种机制，通过该机制Shh配体可以激活响应并否定Hip的细胞自主效应，而Hip仍然可以诱导非细胞自主抑制。
The distribution of Sonic Hedgehog (Shh) is a highly regulated and critical process for development. Several negative feedback mechanisms are in place, including the Shh-induced upregulation of Hedgehog interacting protein (Hhip). Hhip sequesters Shh, leading to a non-cell autonomous inhibition of the pathway. Hhip over-expression has a severe effect on neural tube development, raising the question why normal sites of Hhip expression have a seemingly unimpaired response to Shh. Here we show that while Hhip is able to leave its sites of synthesis to inhibit Shh non-cell autonomously, activation of Smoothened (Smo) drastically increases Hhip internalization and degradation cell autonomously. Although Hhip is unable to cell autonomously inhibit the consequences of Smo activation, it can inhibit the Shh response non-cell autonomously. Our data provide a mechanism by which the Shh ligand can activate the response and negate cell autonomous effects of Hhip, while Hhip can still induce non-cell autonomous inhibition.
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影响因子：
56.9
作者：
Blader, P;Rastegar, S;Strahle, U
通讯作者：
Strahle, U
影响因子：
64.8
作者：
Pampliega, Olatz;Orhon, Idil;Patel, Bindi;Sridhar, Sunandini;Diaz-Carretero, Antonio;Beau, Isabelle;Codogno, Patrice;Satir, Birgit H.;Satir, Peter;Cuervo, Ana Maria
通讯作者：
Cuervo, Ana Maria
影响因子：
16.8
作者：
通讯作者：
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影响因子：
3.5
作者：
Coulombe, J;Traiffort, E;Ruat, M
通讯作者：
Ruat, M
DOI：
10.1073/pnas.220251997
发表时间：
2000-10-24
影响因子：
11.1
作者：
Incardona, JP;Lee, JH;Roelink, H
通讯作者：
Roelink, H