Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d).

Abstract

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.