Primary cilia are specialized calcium signalling organelles.

Primary cilia are specialized calcium signalling organelles.
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DOI:
10.1038/nature12833
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发表时间:
2013-12-12
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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初生纤毛是中心粒在细胞分裂之间几乎所有有核真核细胞上发现的孤立的、不活动的延伸。∼直径200-300 nm,长几微米,由纤毛颈和基底体与细胞质分开。通常被称为感觉纤毛,它们被假设为接受化学和机械刺激,并启动特定的细胞信号转导通路。当被配体激活时,Hedgehog(HH)途径蛋白,如Gli2和Smoothened(Smo),从细胞转移到纤毛。初级纤毛蛋白的突变与严重的发育缺陷有关。离子条件,初级纤毛膜的通透性,以及纤毛和细胞体之间扩散屏障的有效性尚不清楚。在这里,我们表明纤毛是一个独特的钙室,由一个异构体Trp通道,PKD1-L1/PKD2-L1调节。与多囊蛋白(PKD)通道引起纤毛钙离子进入细胞质的变化的假设相反,我们发现纤毛钙离子浓度([Ca2+]纤毛)的变化并没有实质上改变整体胞浆钙离子([Ca2+]Cyto)。PKD1-L1/PKD2-L1作为纤毛钙通道控制纤毛,从而改变Smo激活的Gli2转位和Gli1的表达。
Primary cilia are solitary nonmotile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only ∼200-300 nm in diameter and a few microns long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are hypothesized to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, Hedgehog (Hh) pathway proteins, such as Gli2 and Smoothened (Smo), translocate from the cell into the cilium. Mutations in primary ciliary proteins are associated with severe developmental defects. The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1-L1/PKD2-L1. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm, we show that changes in ciliary calcium concentration ([Ca2+]cilia) occur without substantially altering global cytoplasmic calcium ([Ca2+]cyto). PKD1-L1/PKD2-L1 acts as a ciliary calcium channel controlling [Ca2+]cilia and thereby modifying Smo-activated Gli2 translocation and Gli1 expression.
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