The biological function of PIP2 clustering in enzyme activation and ion channel regulation

Abstract

The signaling lipid phosphatidylcholine 4,5 bisphosphate (PIP2) clusters with proteins in the plasma membrane away from saturated domains formed by GM1 lipids and cholesterol (GM1 domains or ‘lipid rafts’). The lipid metabolizing enzyme phospholipase D2 (PLD2) localizes to both lipid raft and PIP2 clusters creating a competition for localization. We show that disruption of GM1 domains by mechanical force or inhaled anesthetics causes PLD2 to translocate to PIP2 clusters where it activates twik related potassium (TREK‐1) channels giving rise to the channel's mechano and anesthetic sensitivity. We conclude cells have evolved to (i.) sense and respond to disruption of lipid order and (ii.) utilize lipid order to dynamically regulate enzymes and ion channels through substrate presentation.Support or Funding InformationThis work was supported by a Director's New Innovator Award (1DP2NS087943‐01 to S.B.H.) from the NIH, a graduate fellowship from the Joseph B. Scheller & Rita P. Scheller Charitable Foundation to E.N.P. We are grateful to the Iris and Junming Le Foundation for funds to purchase a super‐resolution microscope, making this study possible.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.