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Channels (Austin)
2020 Dec 01;141:1-3. doi: 10.1080/19336950.2020.1778393.
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The Slo3/Lrrc52 complex is sensitive to phosphoinositides.
Kawai T
,
Okamura Y
.
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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)P2 distribution in sperm flagellum. Interestingly, such specialized PtdIns(4,5)P2 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)P2 using a heterologous expression system. However, PtdIns(4,5)P2-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.
Figure 1. Functional coupling between Slo3/Lrrc52 complex with VSP reconstituted in Xenopus oocytes. (a) Lrrc52 drastically changes electrophysiological property of Slo3. Representative traces of Slo3 currents with or without Lrrc52. 100 ms voltage pulses in steps of 10 mV from −80 to +100 mV were applied. Holding potential was −60 mV. I–V relationships for Slo3 currents with (square) or without (circle) Lrrc52. (b) The representative traces of test pulses at +40 mV (Slo3) or −100 mV (Kir2.1) for 50 ms are shown. The test pulses were repeated for 21 times, and depolarization of +50 mV for 300 ms was applied in intervals between test pulses to activate Ci-VSP. The enzyme-defective mutant (Ci-VSP C363S) showed no change in current amplitude, indicating that the reduction of Slo3 or Kir2.1 current was due to enzyme activity of Ci-VSP. Dotted lines indicate the zero current level. (c) Representative data showing time course of relative current amplitude by repetitive VSP activation. The data for VSP+Slo3 was already reported in the previous paper and showed as broken line. (d) Statistical analysis showing inhibition percentage at 21th trials of test pulses. * indicates significant difference: p < 0.05, t-test. (e) The Slo3/Lrrc52 complex is sensitive to PIPs. The activity of Slo3/Lrrc52 complex is upregulated with strong binding of PtdIns(4,5)P2 (Left). After PtdIns(4,5)P2 is dephosphorylated by VSP in voltage-dependent manner, Slo3/Lrrc52 complex is less activated (Right).
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