Abstract
The voltage sensor of ion channels regulates permeation of ions. A protein recently identified from ascidian genome, named as Ci-VSP, contains voltage sensor homologous to ion-channel like voltage sensor and phosphatase domain. Ci-VSP tunes its phosphatase activity depended on membrane potential change. We cloned a similar protein from zebrafish which is homologous to Ci-VSP. Whole-mount in situ hybridization showed that zebrafish VSP (z-VSP) is expressed in gut cells during embryogenesis. The z-VSP shows moderately small amount of Off-gating current when expressed in Xenopus oocyte, whereas its On-gating current was not so robust. Half maximum activation of Off-gating current occurs around at 110 mV, 44mV higher than that of Ci-VSP. Insertion of additional positively charged residue, arginine, in the S4-like segment facilitated the movement of this domain, supporting that S4-like segment of z-VSP operates as the voltage sensor as in Ci-VSP. z-VSP shows voltage-dependent phosphatase activity, as detected by activation of co-expressed KCNQ2,3 channel which is known to be sensitive to PIP2. Despite less robust gating current, z-VSP shares the conserved nature of voltage-dependent tuning of phosphatase activity with Ci-VSP. Therefore, the nature of voltage-dependent phosphatase of VSP is not a rarity to marine invertebrate, but more widespread in the chordates. [Jpn J Physiol 55 Suppl:S130 (2005)]
