Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, NY 10461
B&P Nanobiology Consultants, 7 Byfield Lane, Greenwich, CT 06830, USA.
J Cell Sci. 2019 Aug 2;132(15):jcs230441. doi: 10.1242/jcs.230441.
Many signaling molecules are localized to both the primary cilium and nucleus. Localization of specific transmembrane receptors and their signaling scaffold molecules in the cilium is necessary for correct physiological function. After a specific signaling event, signaling molecules leave the cilium, usually in the form of an endocytic vesicle scaffold, and move to the nucleus, where they dissociate from the scaffold and enter the nucleus to affect gene expression. This ancient pathway probably arose very early in eukaryotic evolution as the nucleus and cilium co-evolved. Because there are similarities in molecular composition of the nuclear and ciliary pores the entry and exit of proteins in both organelles rely on similar mechanisms. In this Hypothesis, we propose that the pathway is a dynamic universal cilia-based signaling pathway with some variations from protists to man. Everywhere the cilium functions as an important organelle for molecular storage of certain key receptors and selection and concentration of their associated signaling molecules that move from cilium to nucleus. This could also have important implications for human diseases such as Huntington disease.
许多信号分子定位于初级纤毛和细胞核。特定跨膜受体及其信号支架分子在纤毛中的定位对于正确的生理功能是必要的。在特定的信号事件发生后，信号分子离开纤毛，通常以网格蛋白小泡的形式，并移动到细胞核，在那里它们与支架分离并进入细胞核影响基因表达。这条古老的途径可能在真核生物进化的早期就出现了，因为核和纤毛是共同进化的。由于核孔和纤毛孔的分子组成相似，蛋白质在这两个细胞器中的进出依赖于相似的机制。在这个假说中，我们提出该途径是一种动态的、普遍存在的基于纤毛的信号通路，在从原生动物到人这一过程中有一些变化。纤毛作为某些关键受体的分子储存器以及它们相关的信号分子的选择和浓缩的重要细胞器，这些信号分子从纤毛转移到细胞核。这对人类疾病，如亨廷顿病，也可能有重要影响。
