Primary cilia are antenna‐like organelles on the surface of most mammalian cells that receive sonic hedgehog (Shh) signaling in embryogenesis and carcinogenesis. Cellular cholesterol functions as a direct activator of a seven‐transmembrane oncoprotein called Smoothened (Smo) and thereby induces Smo accumulation on the ciliary membrane where it transduces the Shh signal. However, how cholesterol is supplied to the ciliary membrane remains unclear. Here, we report that peroxisomes are essential for the transport of cholesterol into the ciliary membrane. Zellweger syndrome (ZS ) is a peroxisome‐deficient hereditary disorder with several ciliopathy‐related features and cells from these patients showed a reduced cholesterol level in the ciliary membrane. Reverse genetics approaches revealed that the GTP exchange factor Rabin8, the Rab GTP ase Rab10, and the microtubule minus‐end‐directed kinesin KIFC 3 form a peroxisome‐associated complex to control the movement of peroxisomes along microtubules, enabling communication between peroxisomes and ciliary pocket membranes. Our findings suggest that insufficient ciliary cholesterol levels may underlie ciliopathies.

中文翻译：

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遗传性Zellweger综合征的睫状胆固醇不足。

初级纤毛是大多数哺乳动物细胞表面上的触角状细胞器，在胚胎发生和致癌过程中会接受声波刺猬（Shh）信号。细胞胆固醇起着称为平滑化（Smo）的七跨膜癌蛋白的直接激活剂的作用，从而诱导Smo在睫状体膜上积累，并在该处转导Shh信号。但是，如何将胆固醇供应到睫状膜尚不清楚。在这里，我们报道过氧化物酶体对于胆固醇进入睫状膜的运输至关重要。Zellweger综合征（ZS）是一种过氧化物酶体缺乏的遗传性疾病，具有一些与睫状体病相关的特征，这些患者的细胞显示出睫状膜中的胆固醇水平降低。反向遗传学方法显示，GTP交换因子Rabin8，Rab GTP酶Rab10，微管负端驱动蛋白KIFC 3形成与过氧化物酶体相关的复合物，以控制过氧化物酶体沿微管的运动，从而使过氧化物酶体与睫状体囊膜之间能够进行通讯。我们的发现表明纤毛胆固醇水平不足可能是纤毛病的基础。