Department of Biomedicine - Physiology, Aarhus University, Ole Worms Allé 6, Building 1180, 8000 Aarhus C, Denmark.
Semin Cell Dev Biol. 2013 Jan;24(1):3-10. doi: 10.1016/j.semcdb.2012.10.003. Epub 2012 Oct 17.
During the last 10 years or so, the renal research community has set the primary cilium into the lime light. From being viewed as a possible evolutionary rudiment, today the primary cilium has achieved the noble status of a physiologically relevant and necessary cellular structure. Its prime function in renal epithelium appears to be its ability to sense urinary flow. Much is still lacking to understand how the primary cilium senses flow. Transducer proteins, such as specific mechano-sensory ion channels, have been identified and are necessary for flow-dependent increases of epithelial Ca(2+). Other ciliary receptor proteins have been suggested, which may open the field of primary cilia sensing to become an even more dynamic topic of research. A flow-induced increase of Ca(2+) has been observed in all renal and other ciliated epithelial cells. Work over the last 5 years has addressed the mechanism underlying the flow-induced increase of Ca(2+). It has become apparent that an initial Ca(2+) influx triggers a global increase of epithelial Ca(2+). Eventually, it also became clear that mechanical stimulation of the epithelial cells triggers the release of ATP. Intriguingly, ATP is an auto- and paracrine signaling molecule that regulates electrolyte and water transport in the nephron by binding to apical and basolateral purinergic receptors. ATP inhibits transport at almost all sites from the proximal to the distal tubule and thus elicits a diuretic response. In the perspective of this review, the primary cilium is a sensory structure and the adequate stimulus is the mechanical deflection. The output signal is the released ATP, a paracrine factor that ultimately modulates the main function of the kidney, i.e. the enormous task of absorbing some 180 L of filtrate every day.
在过去的 10 年左右的时间里，肾脏研究领域将初级纤毛置于聚光灯下。从被视为可能的进化遗迹，到今天，初级纤毛已经获得了作为一种与生理相关且必要的细胞结构的崇高地位。它在肾上皮细胞中的主要功能似乎是感知尿流。要了解初级纤毛如何感知流动，还有很多需要了解。已经鉴定出传感器蛋白，例如特定的机械感觉离子通道，它们是上皮细胞Ca(2+)依赖于流动增加所必需的。还提出了其他纤毛受体蛋白，这可能会使初级纤毛感应领域成为一个更具活力的研究课题。已经在所有肾和其他纤毛上皮细胞中观察到流动诱导的Ca(2+)增加。过去 5 年的工作解决了流动诱导的Ca(2+)增加的机制问题。显然，最初的 Ca(2+)内流触发了上皮细胞Ca(2+)的整体增加。最终，也清楚地表明，机械刺激上皮细胞会触发 ATP 的释放。有趣的是，ATP 是一种自分泌和旁分泌信号分子，通过与顶端和基底外侧嘌呤能受体结合，调节肾单位中的电解质和水转运。ATP 在从近端小管到远端小管的几乎所有部位都抑制转运，从而引发利尿反应。从这个综述的角度来看，初级纤毛是一种感觉结构，适当的刺激是机械偏转。输出信号是释放的 ATP，一种旁分泌因子，最终调节肾脏的主要功能，即每天吸收约 180 升滤液的巨大任务。
