Structures of vertebrate Patched and Smoothened reveal intimate links between cholesterol and Hedgehog signalling
Structures of vertebrate Patched and Smoothened reveal intimate links between cholesterol and Hedgehog signalling
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DOI：
10.1016/j.sbi.2019.05.015
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发表时间：
2019-08-01
影响因子：
6.8
通讯作者：
Siebold, Christian
中科院分区：
文献类型：
--
作者：
Kowatsch, Christiane;Woolley, Rachel E.;Siebold, Christian
刺猬（HH）信号通路是一个细胞通讯系统，控制多细胞动物胚胎发生过程中多种组织的模式。在成人中，HH信号调节组织干细胞和再生反应。异常信号会导致出生缺陷和癌症。HH信号由HH配体的受体Patched（PTCH 1）在靶细胞上接收，然后由Smoothened（SMO）穿过质膜传输。最近的结构和生物化学研究指出，固醇脂质，可能是胆固醇本身，作为难以捉摸的第二信使，在PTCH 1和SMO之间传递HH信号，从而将配体接收与跨膜信号传导联系起来。
The Hedgehog (HH) signalling pathway is a cell cell communication system that controls the patterning of multiple tissues during embryogenesis in metazoans. In adults, HH signals regulate tissue stem cells and regenerative responses. Abnormal signalling can cause birth defects and cancer. The HH signal is received on target cells by Patched (PTCH1), the receptor for HH ligands, and then transmitted across the plasma membrane by Smoothened (SMO). Recent structural and biochemical studies have pointed to a sterol lipid, likely cholesterol itself, as the elusive second messenger that communicates the HH signal between PTCH1 and SMO, thus linking ligand reception to transmembrane signalling.