An epithelial serine protease activates the amiloride-sensitive sodium channel
An epithelial serine protease activates the amiloride-sensitive sodium channel
复制标题
DOI：
10.1038/39329
复制
发表时间：
1997-10-09
期刊：
影响因子：
64.8
通讯作者：
Rossier, BC
中科院分区：
文献类型：
--
作者：
Vallet, V;Chraibi, A;Rossier, BC
通过精确调节上皮钠通道（ENaC）的活性来维持钠平衡，并最终维持血压和细胞外液量（1-3）。在非洲爪蟾肾上皮细胞系（A6）中，顶膜暴露于蛋白酶抑制剂抑肽酶可减少跨上皮钠转运。钠通道活性可以通过随后暴露于非特异性蛋白酶胰蛋白酶来恢复。使用A6细胞和功能互补试验检测ENaC活性的增加，我们克隆了一个329个残基的蛋白质属于丝氨酸蛋白酶家族。我们发现，这种蛋白质与ENaC在非洲爪蟾卵母细胞的共表达增加了两到三倍的钠通道的活性。这种通道激活蛋白酶（CAP 1）在肾脏、肠道、肺、皮肤和卵巢中表达。序列分析预测，CAP 1是一种分泌的和/或糖基磷脂酰肌醇锚定蛋白：ENaC活性因此将受到同一细胞表面表达的蛋白酶活性的调节。这种以前未发现的自分泌调节机制可能适用于其他离子通道，特别是存在于神经元和上皮细胞中的ENaC家族成员。
Sodium balance, and ultimately blood pressure and extracellular fluid volume, is maintained by precise regulation of the activity of the epithelial sodium channel (ENaC)(1-3). In a Xenopus kidney epithelial cell Line (A6), exposure of the apical membrane to the protease inhibitor aprotinin reduces transepithelial sodium transport. Sodium-channel activity can be restored by subsequent exposure to the nonspecific protease trypsin. Using A6 cells and a functional complementation assay to detect increases in ENaC activity, we have cloned a 329-residue protein belonging to the serine protease family. We show that coexpression of this protein with ENaC in Xenopus oocytes increases the activity of the sodium channel by two- to threefold. This channel-activating protease (CAP1) is expressed in kidney, gut, lung, skin and ovary. Sequence analysis predicts that CAP1 is a secreted and/or glycosylphosphatidylinositol-anchored protein: ENaC activity would thus be regulated by the activity of a protease expressed at the surface of the same cell. This previously undiscovered mechanism for autocrine regulation may apply to other ion channels, in particular to members of the ENaC family that are present in neurons and epithelial cells.