初级纤毛不是钙反应性机械传感器。
Primary cilia are not calcium-responsive mechanosensors.
作者信息
Delling M, Indzhykulian A A, Liu X, Li Y, Xie T, Corey D P, Clapham D E
机构信息
Department of Cardiology, Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Nature. 2016 Mar 31;531(7596):656-60. doi: 10.1038/nature17426. Epub 2016 Mar 23.
Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium. This Ca(2+)-responsive mechanosensor hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers. Here we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. We developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca(2+) influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signalling.
初级纤毛是单个的、通常无运动能力的毛发状突起,在细胞分裂间期从细胞表面伸出。它们类似触角的结构自然而然地让人认为它们能感知周围环境,最常见的假说是通过纤毛内的钙通透离子通道感知机械力。这种关于初级纤毛的钙响应机械传感器假说已被用于解释从胚胎发育中左右轴确定的控制到多囊肾病和某些癌症的成人进展等一系列生物学反应。在此,我们报告在该假说所基于的组织中,初级纤毛完全不存在机械诱导的钙增加。我们构建了一种转基因小鼠,Arl13b-mCherry-GECO1.2,其在所有初级纤毛中表达一种比率型基因编码钙指示剂。然后我们测量了培养的肾上皮细胞、肾髓袢升支粗段、胚胎节点的冠细胞、内耳毛细胞的动纤毛以及几种细胞系的初级纤毛对流动的反应。在生理甚至高度超生理水平的流体流动中均未观察到纤毛特异性的钙内流。我们得出结论,机械感觉如果起源于初级纤毛,并非通过钙信号传导。