Hedgehog interacting protein in the mature brain: membrane-associated and soluble forms
Hedgehog interacting protein in the mature brain: membrane-associated and soluble forms
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DOI：
10.1016/j.mcn.2003.10.024
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发表时间：
2004-02-01
影响因子：
3.5
通讯作者：
Ruat, M
中科院分区：
文献类型：
--
作者：
Coulombe, J;Traiffort, E;Ruat, M
刺猬相互作用蛋白（Hip）被认为是一种膜蛋白，在胚胎发育过程中与刺猬（hh）形态发生蛋白的隔离有关。在这里，我们表明，髋关节转录也发生在分散在离散的成年啮齿类动物的大脑区域的细胞，我们确定了膜相关的和可溶性形式的髋关节在成熟的大脑中的存在。此外，我们表明，可溶性形式的髋关节，目前在HEK 293细胞过度表达髋关节的条件培养基，抑制声刺猬（Shh）诱导分化的C3 H10 T1/2细胞，一个良好的特征响应与Shh信号。在HEK 293细胞中转染后，在密度梯度离心期间，Hip与筏组分神经节苷脂GM 1分配。标记的髋关节结构的分析表明，髋关节的假定跨膜结构域不裂解，这表明其他机制涉及其可溶性形式的释放。两者合计，这些数据是一致的参与膜相关和可溶性髋关节在成年神经组织中的调节Shh信号。(C)2004年爱思唯尔公司All rights reserved.
Hedgehog interacting protein (Hip) is considered as a membrane protein implicated in sequestering the hedgehog (hh) morphogens during embryonic development. Here, we demonstrate that Hip transcription also occurs in cells scattered in discrete brain areas of adult rodents and we identify the presence of membrane-associated and soluble forms of Hip in the mature brain. Moreover, we show that soluble forms of Hip, present in the conditioned medium of HEK293 cells overexpressing Hip, inhibit Sonic hedgehog (Shh)-induced differentiation of C3H10T1/2 cells, a well-characterised response associated with Shh signalling. After transfection in HEK293 cells, Hip partitions with the raft component ganglioside GM1 during density gradient centrifugation. Analysis of tagged Hip constructs reveals that the putative transmembrane domain of Hip is not cleaved suggesting that other mechanisms are implicated in the release of its soluble forms. Taken together, these data are consistent with the involvement of both membrane-associated and soluble Hip in the regulation of Shh signalling in adult neural tissues. (C) 2004 Elsevier Inc. All rights reserved.