Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d).
Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d).
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DOI：
10.17912/micropub.biology.000412
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发表时间：
2021-06-21
影响因子：
--
通讯作者：
Bianchi L
中科院分区：
文献类型：
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作者：
Johnson CK;Miller DD;Bianchi L
线虫 MEC-4 和 UNC-8 属于电压无关的 Na+ 通道 DEG/ENaC 家族，与机械感觉和突触重塑有关。 MEC-4 和 UNC-8 高度活跃的突变体，指定为 (d) 突变体，传导增强的电流并由于不受控制的阳离子流入而导致细胞死亡。我们在此表明，用蛋白酶纤溶酶处理可进一步增强 MEC-4(d) 而不是 UNC-8(d) 电流，并且这种效果取决于与伴侣蛋白 MEC-6 的共表达。哺乳动物 DEG/ENaC 通道在通道指结构域中被纤溶酶切割，MEC-4 和 UNC-8 在该结构域中都有预测的纤溶酶切割位点。我们之前表明，MEC-4(d)（而非 UNC-8(d））电流通过与 MEC-6 共表达而增加，MEC-6 通过指状结构域与通道相互作用。我们认为通道亚基与 MEC-6 的相互作用可能使纤溶酶切割位点更容易接近。鉴于线虫表达纤溶酶同源物，这些效应可能与体内相关。
C. elegans MEC-4 and UNC-8 belong to the DEG/ENaC family of voltage-independent Na+ channels and have been implicated in mechanosensation and synaptic remodeling. MEC-4 and UNC-8 hyperactive mutants, designated (d) mutants, conduct enhanced currents and cause cell death due to uncontrolled influx of cations. We show here that MEC-4(d) but not UNC-8(d) currents are further potentiated by treatment with the protease plasmin and that this effect is dependent upon co-expression with the chaperon protein MEC-6. Mammalian DEG/ENaC channels are cleaved by plasmin in the channel finger domain and both MEC-4 and UNC-8 have a predicted plasmin cleavage site in this domain. We previously showed that MEC-4(d), but not UNC-8(d), currents are increased by co-expression with MEC-6, which interacts with the channel via the finger domain. We suggest that interaction of the channel subunit with MEC-6 may render the plasmin cleavage site more accessible. Given that C. elegans expresses a homolog of plasmin, these effects might be relevant in vivo.