Functional interaction between autophagy and ciliogenesis

摘要

初级纤毛是一种非运动性信号作用细胞器，见于胞质膜的一个特定区域，在那里它发挥两个功能：信号传导和探测环境提示如营养物水平等。本期Nafure上发表的两篇互补的论文描述了纤毛生成与自吞作用之间的一个新颖联系。Zaiming Tang等人发现，在"中心粒随体"上发生的纤毛形成过程的一个负调控因子（即"oral-facial-digital syndrome 1",缩写为 0FD1)的自吞降解，促进初级纤毛的生物生成。Olatz Pampliega等人揭示了纤毛生成与自吞作用之间的一个互惠关系，发现初级纤毛是由饥饿诱导的自吞作用的激发所需的，而且自吞作用负调控纤毛生成。初级纤毛和自吞作用通道之间的"交流"也许会进而导致我们对人类纤毛疾病的认识。%Nutrient deprivation is a stimulus shared by both autophagy and the formation of primary cilia. The recently discovered role of primary cilia in nutrient sensing and signalling motivated us to explore the possible functional interactions between this signalling hub and autophagy. Here we show that part of the molecular machinery involved in ciliogenesis also participates in the early steps of the autophagic process. Signalling from the cilia, such as that from the Hedgehog pathway, induces autophagy by acting directly on essential autophagy- related proteins strategically located in the base of the cilium by ciliary trafficking proteins. Whereas abrogation of ciliogenesis partially inhibits autophagy, blockage of autophagy enhances primary cilia growth and cilia-associated signalling during normal nutritional conditions. We propose that basal autophagy regulates ciliary growth through the degradation of proteins required for intraflagellar transport. Compromised ability to activate the autophagic response may underlie some common ciliopathies.