The Slo3/Lrrc52 complex is sensitive to phosphoinositides

The voltage-sensing phosphatase (VSP) is a unique protein that shows voltage-dependent phosphatase activity toward phosphoinositides. Recently, we reported that VSP is activated and generates polarized PtdIns(4,5)P(2) distribution in sperm flagellum. Interestingly, such specialized PtdIns(4,5)P(2) distribution appears to contribute to the activity of Slo3, a sperm-specific K(+) channels. It has been already reported that Slo3 activity is upregulated by PtdIns(4,5)P(2) using a heterologous expression system. However, PtdIns(4,5)P(2)-dependence of Slo3 activity has not been studied in heterologous expression system in the presence of auxiliary subunit of Slo3, Lrrc52, which drastically changes the electrophysiological property of Slo3. In the present study, we analyzed the regulation of Slo3 activity with Lrrc52 by VSP in Xenopus oocytes. Slo3 with Lrrc52 still exhibited similar sensitivity to VSP activity as Slo3 alone. This finding supports our previous report that VSP regulates Slo3 activity in native sperm flagellum.