Hitching a ride to the top: peroxisomes fuel cilium with cholesterol

Hitching a ride to the top: peroxisomes fuel cilium with cholesterol
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搭便车登上顶峰:过氧化物酶体为纤毛提供胆固醇

DOI:
10.1007/s11427-020-1866-8
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发表时间:
2021-01
期刊:
Science China Life Sciences
影响因子:
--
通讯作者:
Song Bao-Liang
Song Bao-Liang
中科院分区:
其他
文献类型:
--
作者:
Luo Jie;Liu Yuan-Bin;Song Bao-Liang

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初级纤毛是一种以微管为基础的结构,由高度特化的质膜(PM)包裹。它是感知和传递各种外界刺激的信号中枢,包括流体、光、气味以及细胞外分子。在通过初级纤毛的各种信号转导途径中,Hedgehog(HH)途径最受关注,因为它在脊椎动物发育中起重要作用,并与癌症发生密切相关(Bangs和Anderson,2017)。HH途径的主要成分包括分泌的配体HH,两种跨膜蛋白Patch(Ptch)和Smoothened(Smo),和转录因子胶质瘤相关癌基因(Gli)。Ptch是HH的受体,在没有HH的情况下,它位于初级纤毛,阻止Smo的纤毛定位和激活。然而,一旦HH结合,Ptch被抑制并从睫状膜移位。这允许Smo进入初级纤毛,启动一连串的事件,导致Gli转录因子的激活和下游靶基因的转录。
Primary cilium,which protrudes from the cell,is a microtubule- based structure ensheathed by a highly specialized plasma membrane (PM).It serves as a signaling hub for sensing and transducing various external stimuli including fluids,light,odorants as well as extracellular molecules.Of various signal transduction pathways that act through the primary cilium,the Hedgehog (Hh) pathway draws the most attention owing to its essential role in vertebrate development and its intimate link to carcinogenesis (Bangs and Anderson,2017).The major components of the Hh pathway include the secreted ligand Hh,two transmembrane proteins Patched (Ptch) and Smoothened (Smo),and the transcription factor glioma-associated oncogene (Gli).Ptch is the receptor for Hh which,in the absence of Hh,resides at the primary cilium and prevents ciliary localization and activation of Smo.Upon Hh binding,however,Ptch is suppressed and displaced from the ciliary membrane.This permits Smo to enter the primary cilium and initiate a cascade of events that lead to the activation of Gli transcription factors and transcription of downstream target genes.
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