Science Topics - 94

Voltage-sensing phosphatase (VSP) consists of a voltage sensor domain and the cytoplasmic phosphatase domain. The phosphatase domain has the activity to dephosphorylate phosphoinositides in response to the movement of the voltage sensor. In 2011, we have measured the voltage-dependent phosphatase activity quantitatively and found that the phosphatase activity is tightly coupled to the movement of the voltage sensor (Sakata et al.,J.Physiol.,2011). This result raises two possibilities about the coupling mechanism between the phosphatase activity and the voltage sensor movement at the single molecule level. One is that the phosphatase activity is exhibited only when the voltage sensor is fully activated, and the voltage-dependency of the phosphatase activity represents the transition of population of the fully-activated VSP molecules. The other is that the phosphatase activity is graded at the single protein level, and the magnitude of the phosphatase activity is associated with that of the movement of the voltage sensor. To distinguish these possibilities, we made the voltage sensor mutant whose voltage sensor has a stable intermediate state between the fully activated state and the resting state. The measurements of the phosphatase activity revealed that this mutant has the phosphatase activity even in the intermediate state of the voltage sensor. This demonstrates that VSP does not need the full activation of the voltage sensor for the exhibition of the phosphatase activity and suggests that the magnitude of the phosphatase activity is associated with that the extent or mode of movement of the voltage sensor. (J.Physiol. 592:899-914,2014; introduced by “Perspective” article on the same volume of the journal).

Figure. The phosphatase activity of voltage-sensing phosphatase (VSP) regulated by the movement of the voltage sensor. This study revealed that, at the single molecule level, the phosphatase activity of VSP is graded and the magnitude of the activity depends on the magnitude or mode of the movement of the voltage sensor. 

  1Integrative Physiology, Graduate School of Medicine, Osaka University, 2Institute for Academic Initiative, Osaka University