The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.
The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.
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DOI：
10.1371/journal.pgen.1002864
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Chuang CF
中科院分区：
文献类型：
--
作者：
Hsieh YW;Chang C;Chuang CF
秀丽隐杆线虫左右 AWC 嗅觉神经元通过抑制未来 AWCON 细胞中钙介导的信号通路来进行通信，以建立随机不对称身份 AWCON 和 AWCOFF。 NSY-4/claudin 样蛋白和 NSY-5/innexin 间隙连接蛋白是拮抗钙信号通路以诱导 AWCON 命运的两个平行信号。然而，尚不清楚 AWCON 细胞中 NSY-4 和 NSY-5 如何下调钙信号通路。在这里，我们鉴定了一种 microRNA，mir-71，它抑制钙信号通路中的 TIR-1/Sarm1 接头蛋白，以促进 AWCON 身份。与 tir-1 功能丧失突变体类似，mir-71 的过度表达会产生两个 AWCON 神经元。 tir-1 的表达在 AWCON 中通过其 3' UTR 下调，其中 mir-71 的表达水平高于 AWCOFF 中。此外，mir-71 足以通过 tir-1 3' UTR 中的 mir-71 互补位点抑制 AWC 中 tir-1 的表达。我们的遗传学研究表明，mir-71 在 nsy-4 和 nsy-5 下游发挥作用，以细胞自主方式促进 AWCON 身份。此外，成熟的mir-71的稳定性依赖于nsy-4和nsy-5。总之，这些结果提供了对 nsy-4 和 nsy-5 抑制钙信号传导以建立随机不对称 AWC 分化的机制的深入了解。细胞身份的确定需要细胞类型特异性基因的诱导和促进替代细胞类型的基因的抑制之间的竞争。在线虫秀丽隐杆线虫中，特定的感觉神经元对进行通信，通过抑制神经元中成为诱导身份的钙信号传导途径来建立随机不对称身份。然而，目前尚不清楚细胞间通讯如何抑制诱导神经元身份中的钙信号通路。在这项研究中，我们鉴定了一种 microRNA，它可以抑制钙信号通路中关键分子的表达，从而促进诱导的神经元身份。 microRNA 的过度表达导致该对的两个神经元都变成诱导身份，类似于钙信号传导通路中失去功能的突变体。此外，成熟microRNA的稳定性依赖于紧密蛋白样蛋白和间隙连接蛋白，这两个平行信号介导神经元对的通讯以促进诱导的神经元同一性。我们的结果提供了对细胞间通讯抑制钙信号传导以建立随机不对称神经元分化的机制的见解。
The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWCON and AWCOFF, by inhibiting a calcium-mediated signaling pathway in the future AWCON cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWCON fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWCON cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWCON identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWCON neurons. tir-1 expression is downregulated through its 3′ UTR in AWCON, in which mir-71 is expressed at a higher level than in AWCOFF. In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3′ UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWCON identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation. Cell identity determination requires a competition between the induction of cell type–specific genes and the suppression of genes that promote an alternative cell type. In the nematode C. elegans, a specific sensory neuron pair communicates to establish stochastic asymmetric identities by inhibiting a calcium signaling pathway in the neuron that becomes an induced identity. However, it is not understood how cell–cell communication inhibits the calcium signaling pathway in the induced neuronal identity. In this study, we identify a microRNA that represses the expression of a key molecule in the calcium signaling pathway to promote the induced neuronal identity. Overexpression of the microRNA causes both neurons of the pair to become the induced identity, similar to the mutants that lose function in the calcium signaling pathway. In addition, the stability of the mature microRNA is dependent on a claudin-like protein and a gap junction protein, the two parallel signals that mediate communication of the neuron pair to promote the induced neuronal identity. Our results provide insight into the mechanism by which cell–cell communication inhibits calcium signaling to establish stochastic asymmetric neuronal differentiation.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
9.2
作者：
Colosimo, ME;Brown, A;Sengupta, P
通讯作者：
Sengupta, P
影响因子：
10.5
作者：
Chuang, CF;Bargmann, CI
通讯作者：
Bargmann, CI
影响因子：
16.2
作者：
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通讯作者：
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影响因子：
11.8
作者：
Abbott, AL;Alvarez-Saavedra, E;Ambros, V
通讯作者：
Ambros, V