Nematode homologs of the sour taste receptor Otopetrin1 are evolutionarily conserved acid-sensitive proton channels.
Nematode homologs of the sour taste receptor Otopetrin1 are evolutionarily conserved acid-sensitive proton channels.
复制标题
酸味受体 Otopetrin1 的线虫同源物是进化上保守的酸敏感质子通道。
DOI：
10.3389/fcell.2023.1133890
复制
发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
在脊椎动物和无脊椎动物中已经鉴定出许多味觉受体和相关分子。Otopetrin 1是哺乳动物的酸味受体，与酸的感觉有关。然而，其他Otopetrin蛋白是否参与PH传感仍然未知。In C.在线虫中，otopetrin有8个同源基因，但其表达模式和功能尚未见报道。通过在HEK 293 T细胞中的异源表达，我们发现ceOTOP 1a可以在没有常规阳离子的NMDG+溶液中被酸激活，产生内向电流，并且可以被锌离子阻断。此外，我们发现，Otopetrin通道在许多组织中广泛表达，特别是在线虫的感觉神经元中。这些结果表明，线虫中的Otopetrin通道的生物物理特性通常是保守的。然而，通过CRISPR-Cas9方法构建的一系列otopetrin单基因突变并不影响ASH多模态感觉神经元对酸刺激的钙反应或酸回避行为，这表明Otopetrin通道可能在物种之间具有不同的功能。本研究揭示了线虫Otopetrin是进化上保守的酸敏感质子通道，为进一步揭示Otopetrin通道在无脊椎动物和脊椎动物中的功能和机制提供了框架。
Numerous taste receptors and related molecules have been identified in vertebrates and invertebrates. Otopetrin1 has recently been identified as mammalian sour taste receptor which is essential for acid sensation. However, whether other Otopetrin proteins are involved in PH-sensing remains unknown. In C. elegans, there are eight otopetrin homologous genes but their expression patterns and functions have not been reported so far. Through heterologous expression in HEK293T cells, we found that ceOTOP1a can be activated by acid in NMDG+ solution without conventional cations, which generated inward currents and can be blocked by zinc ions. Moreover, we found that Otopetrin channels are widely expressed in numerous tissues, especially in sensory neurons in the nematode. These results suggest that the biophysical characteristics of the Otopetrin channels in nematodes are generally conserved. However, a series of single gene mutations of otopetrins, which were constructed by CRISPR-Cas9 method, did not affect either calcium responses in ASH polymodal sensory neurons to acid stimulation or acid avoidance behaviors, suggesting that Otopetrin channels might have diverse functions among species. This study reveals that nematode Otopetrins are evolutionarily conserved acid-sensitive proton channels, and provides a framework for further revealing the function and mechanisms of Otopetrin channels in both invertebrates and vertebrates.
登录
查看更多内容
DOI：
10.1073/pnas.1013664107
发表时间：
2010-12-21
影响因子：
11.1
作者：
Chang, Rui B.;Waters, Hang;Liman, Emily R.
通讯作者：
Liman, Emily R.
影响因子：
3.5
作者：
Kim, Euysoo;Hyrc, Krzysztof L.;Ornitz, David M.
通讯作者：
Ornitz, David M.
影响因子：
2.8
作者：
Ornitz, DM;Bohne, BA;Thalmann, R
通讯作者：
Thalmann, R
影响因子：
64.5
作者：
Hu, Meiqin;Li, Ping;Wang, Ce;Feng, Xinghua;Geng, Qi;Chen, Wei;Marthi, Matangi;Zhang, Wenlong;Gao, Chenlang;Reid, Whitney;Swanson, Joel;Du, Wanlu;Hume, Richard, I;Xu, Haoxing
通讯作者：
Xu, Haoxing
DOI：
10.1073/pnas.2110641118
发表时间：
2021-12-21
影响因子：
11.1
作者：
Ganguly A;Chandel A;Turner H;Wang S;Liman ER;Montell C
通讯作者：
Montell C