Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelial sodium channels.
Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelial sodium channels.
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DOI：
10.1113/jp283238
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发表时间：
2023-05
影响因子：
5.5
通讯作者：
Walker, Denise S.
中科院分区：
文献类型：
--
作者：
Kaulich, Eva;McCubbin, Patrick T. N.;Schafer, William R.;Walker, Denise S.
酸敏感离子通道（ASIC）是变性蛋白/上皮钠通道（DEG/ENaC）的不同家族的成员。它们在健康生物体中发挥广泛的生理作用，包括肠道功能和突触传递，但也在疾病中发挥重要作用，因为酸中毒是疼痛性炎症和缺血性疾病的标志。我们在爪蟾卵母细胞中使用双电极电压钳对秀丽隐杆线虫DEG/ENaC家族的所有30个亚基进行了酸敏感性筛选。我们发现了两组酸敏感的DEG/ENaC，其特征在于通过增加质子浓度来抑制或激活。三个酸敏感的C elegans DEG/ENaCs被酸性pH激活，使它们在功能上与脊椎动物ASIC相似。我们还确定了酸抑制DEG/ENaC组的三个新成员，总共提供了七个额外的酸敏感通道。我们观察了抗高血压药物阿米洛利的敏感性以及微量元素锌的调节作用。发现酸敏感性DEG/ENaC在神经元和非神经元组织中表达，突出了这些通道可能的功能多样性。我们的研究结果提供了一个框架，利用C。elegans通道作为模型来研究这些酸敏感通道在体内的功能，以及研究它们作为抗蠕虫药物的潜在靶点。 酸中毒在健康生理学中起着许多作用，包括突触传递和肠道功能，但也是炎性疼痛，缺血和许多其他疾病的关键特征。细胞通过pH传感通道（包括酸敏感离子通道（ASIC））监测周围环境的酸中毒。这些是退化蛋白/上皮钠通道（DEG/ENaC）家族的成员，如名称所示，与脊椎动物ENaC和线虫秀丽隐杆线虫的退化蛋白一起沿着。通过筛选所有30个C。在elegans DEG/ENaCs的pH依赖性研究中，我们首次描述了三个酸激活的成员，以及三个额外的酸抑制通道。我们调查了这两组对阿米洛利和锌的敏感性;与哺乳动物类似物一样，它们的电流可以被这些调节剂阻断、增强或不受影响。同样，它们表现出不同的离子选择性。我们的研究结果强调了不同物种间酸敏感DEG/ENaC的多样性，并为更好地理解其功能的分子基础提供了比较资源。 图注DEG/ENaC超科代表性成员的极面示意图，根据门的颜色（环节动物，黄色;节肢动物，浅绿绿色;脊索动物，深绿绿色;刺胞动物，蓝色;软体动物，深紫色;线虫动物，洋红;介壳虫，红色）。图1描述了该图的构造。黑色和灰色方框表示C。elegans酸激活和酸抑制成员。
Acid‐sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). They perform a wide range of physiological roles in healthy organisms, including in gut function and synaptic transmission, but also play important roles in disease, as acidosis is a hallmark of painful inflammatory and ischaemic conditions. We performed a screen for acid sensitivity on all 30 subunits of the Caenorhabditis elegans DEG/ENaC family using two‐electrode voltage clamp in Xenopus oocytes. We found two groups of acid‐sensitive DEG/ENaCs characterised by being either inhibited or activated by increasing proton concentrations. Three of these acid‐sensitive C. elegans DEG/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified three new members of the acid‐inhibited DEG/ENaC group, giving a total of seven additional acid‐sensitive channels. We observed sensitivity to the anti‐hypertensive drug amiloride as well as modulation by the trace element zinc. Acid‐sensitive DEG/ENaCs were found to be expressed in both neurons and non‐neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit the C. elegans channels as models to study the function of these acid‐sensing channels in vivo, as well as to study them as potential targets for anti‐helminthic drugs. Acidosis plays many roles in healthy physiology, including synaptic transmission and gut function, but is also a key feature of inflammatory pain, ischaemia and many other conditions. Cells monitor acidosis of their surroundings via pH‐sensing channels, including the acid‐sensing ion channels (ASICs). These are members of the degenerin/epithelial sodium channel (DEG/ENaC) family, along with, as the name suggests, vertebrate ENaCs and degenerins of the roundworm Caenorhabditis elegans. By screening all 30 C. elegans DEG/ENaCs for pH dependence, we describe, for the first time, three acid‐activated members, as well as three additional acid‐inhibited channels. We surveyed both groups for sensitivity to amiloride and zinc; like their mammalian counterparts, their currents can be blocked, enhanced or unaffected by these modulators. Likewise, they exhibit diverse ion selectivity. Our findings underline the diversity of acid‐sensitive DEG/ENaCs across species and provide a comparative resource for better understanding the molecular basis of their function. Abstract figure legend Polar view of a phylogram of representative members of the DEG/ENaC superfamily, coloured according to phylum (Annelida, yellow; Arthropoda, light green; Chordata, dark green; Cnidaria, blue; Mollusca, dark purple; Nematoda, magenta; Placozoa, red). Construction of the phylogram is described in Fig. 1. Black and grey boxes indicate C. elegans acid‐activated and acid‐inhibited members, respectively.
ENAC选择性滤波器突变体的渗透性特性。
影响因子：
3.8
作者：
Kellenberger, S;Auberson, M;Gautschi, I;Schneeberger, E;Schild, L
通讯作者：
Schild, L
ENAC/DEG家族中的离子选择性：具有支持分析的系统评价。
影响因子：
5.6
作者：
Vallée C;Howlin B;Lewis R
通讯作者：
Lewis R
DOI：
10.1085/jgp.202012655
发表时间：
2021-04-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Fechner S;D'Alessandro I;Wang L;Tower C;Tao L;Goodman MB
通讯作者：
Goodman MB