Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
FASEB J. 2023 Dec;37(12):e23300. doi: 10.1096/fj.202301943R.
Primary cilium is a specialized sensory organelle that transmits environmental information into cells. Its length is tightly controlled by various mechanisms such as the frequency or the cargo size of the intraflagellar transport trains which deliver the building materials such as tubulin subunits essential for the growing cilia. Here, we show the sialoglycan interacting galectin 8 regulates the process of primary ciliogenesis. As the epithelia become polarized, there are more galectin 8 being apically secreted and these extracellular galectin 8 molecules apparently bind to a lipid raft enriched domain at the base of the primary cilia through interacting with lipid raft components, such as GD3 ganglioside and scaffold protein caveolin 1. Furthermore, the binding of galectin 8 at this critical region triggers rapid growth of primary cilia by perturbing the barrier function of the transition zone (TZ). Our study also demonstrates the functionality of this barrier depends on intact organization of lipid rafts at the cilia as genetically knockout of Cav1 and pharmacologically inhibition of lipid raft both phenocopy the effect of apical addition of recombinant galectin 8; that is, rapid elongation of primary cilia and redistribution of cilia proteins from TZ to the growing axoneme. Indeed, as cilia elongated, endogenous galectin 8, caveolin 1, and TZ component, TMEM231, also transited from the TZ to the growing axoneme. We also noted that the interaction between caveolin 1 and TMEM231 could be perturbed by exogenous galectin 8. Taken together, we proposed that galectin 8 promoted primary cilia elongation through impeding the barrier function of the TZ by interfering with the interaction between caveolin 1 and TMEM231.
初级纤毛是一种专门的感觉细胞器，它将环境信息传递到细胞内。其长度受多种机制的严格控制，例如鞭毛内运输列车的频率或货物大小，这些运输列车运送用于生长纤毛的必需建筑材料，如微管亚基。在这里，我们展示了唾液酸糖蛋白相互作用的半乳糖凝集素 8 调节初级纤毛发生的过程。随着上皮细胞极化，更多的半乳糖凝集素 8 被顶端分泌，这些细胞外的半乳糖凝集素 8 分子显然通过与脂质筏成分，如 GD3 神经节苷脂和支架蛋白 caveolin 1 相互作用，结合到初级纤毛底部的富含脂质筏的区域。此外，半乳糖凝集素 8 在这个关键区域的结合通过扰乱过渡区 (TZ) 的屏障功能触发初级纤毛的快速生长。我们的研究还表明，这个屏障的功能取决于纤毛上脂质筏的完整组织，因为 Cav1 的基因敲除和脂质筏的药理学抑制都模拟了顶端添加重组半乳糖凝集素 8 的效果；即，初级纤毛的快速伸长和纤毛蛋白从 TZ 到生长轴突的重新分布。事实上，随着纤毛伸长，内源性半乳糖凝集素 8、caveolin 1 和 TZ 成分 TMEM231 也从 TZ 转移到生长的轴突。我们还注意到，外源性半乳糖凝集素 8 可以干扰 caveolin 1 和 TMEM231 之间的相互作用。综上所述，我们提出半乳糖凝集素 8 通过干扰 caveolin 1 和 TMEM231 之间的相互作用，阻碍 TZ 的屏障功能，从而促进初级纤毛的伸长。
