Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Glia. 2011 Feb;59(2):333-44. doi: 10.1002/glia.21105.
Sensing extracellular milieu is a fundamental requirement of cells. To facilitate and specify sensory reception, mammalian cells develop an antenna-like structure denoted as the primary cilia. Nearly all interphase and nondividing cells in vertebrates have a single, nonmotile seemingly unspecialized cilium (called a primary cilium). In the central nervous system, astrocytes express primary cilia, but their function in astrocytes has not been examined. Recent studies have shown that primary cilia unite receptors and the machinery of signal-transduction components, such as Wnt and Hedgehog (Hh) signaling cascades. Although, Hh signaling cascades are known to be activated in various cells during development, their physiological functions in the adult nervous system, especially in glial cells, are still unknown. In this study, we reveal that glial primary cilia receive the Hh signal and regulate the survival of astrocytes under stressed conditions such as starvation. Interestingly, increased astrocyte survival was reversed by knockdown of Ift20, which is one of the main components for building primary cilia. These results collectively indicate that the activation of Hh signaling in the primary cilia plays an important role in the survival of astrocytes under stressed conditions.
感知细胞外环境是细胞的基本要求。为了促进和特化感觉接收，哺乳动物细胞会发育出一种类似天线的结构，称为初级纤毛。脊椎动物中几乎所有的间期中的和非分裂细胞都有一个单一的、非运动的、看似非特化的纤毛（称为初级纤毛）。在中枢神经系统中，星形胶质细胞表达初级纤毛，但它们在星形胶质细胞中的功能尚未被研究。最近的研究表明，初级纤毛将受体和信号转导成分的机制，如 Wnt 和 Hedgehog（Hh）信号通路，连接起来。尽管 Hh 信号通路在发育过程中已知在各种细胞中被激活，但它们在成年神经系统中的生理功能，特别是在神经胶质细胞中的功能仍然未知。在这项研究中，我们揭示了神经胶质细胞的初级纤毛接收 Hh 信号，并调节星形胶质细胞在饥饿等应激条件下的存活。有趣的是，增加的星形胶质细胞存活率被 Ift20 的敲低所逆转，Ift20 是构建初级纤毛的主要成分之一。这些结果共同表明，Hh 信号在初级纤毛中的激活在应激条件下星形胶质细胞的存活中发挥着重要作用。
