PI(4,5)P2 and L-type Ca2+ Channels Partner Up to Fine-Tune Ca2+ Dynamics in β Cells  Byung-Chang Suh, Jun-Hee Yeon, Cheon-Gyu Park  Cell Chemical Biology  Volume 23, Issue 7, Pages 753-755 (July 2016) DOI: 10.1016/j.chembiol.2016.07.001 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Diagram of CaV Channel Regulation by Membrane PI(4,5)P2 (A) A normal level of plasma membrane PI(4,5)P2 is responsible for the suppression of KATP channel by ATP, activation of L-type CaV channels by membrane depolarization, and vesicle fusion when intracellular Ca2+ was elevated. PI(4,5)P2 is known to directly interact with ion channel proteins and make them fully functional. PI(4,5)P2 also interacts with vesicle proteins for the insulin vesicle fusion with the plasma membrane. When the PI(4,5)P2 is depleted, the sensitivity of KATP channels by ATP is decreased and the activity of CaV channels and vesicle fusion with the plasma membrane are suppressed. So far, the molecular mechanism by which membrane PI(4,5)P2 regulate L-type CaV channels remains unclear. (B) PI(4,5)P2-dependent regulation of CaV channels depends on the coupled CaV β subunit. The PI(4,5)P2 sensitivity of each CaV channel is regulated by the CaV β subunit, in which channels with cytosolic β subunits show relatively higher sensitivity to PI(4,5)P2 depletion. It is postulated that membrane-associated β subunits, such as β2a and β2e, decrease the PI(4,5)P2-sensitivity of CaV channels by decreasing the interaction of the channel pore protein with membrane PI(4,5)P2. In HEK293-derived tsA201 expression systems, high-voltage-activated CaV channels with membrane-associated β subunit show less than 10% of PI(4,5)P2 sensitivity, whereas channels with cytosolic β subunits exhibits more than 30% suppression by PI(4,5)P2 depletion. Low-voltage-activated T-type channels do not need ancillary subunits and are insensitive to PI(4,5)P2 depletion. Cell Chemical Biology 2016 23, 753-755DOI: (10.1016/j.chembiol.2016.07.001) Copyright © 2016 Elsevier Ltd Terms and Conditions