Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid Academic Article uri icon

Overview

MeSH Major

  • Phosphatidic Acids
  • Phospholipase D
  • Potassium Channels, Tandem Pore Domain

abstract

  • Membrane lipids serve as second messengers and docking sites for proteins and play central roles in cell signaling. A major question about lipid signaling is whether diffusible lipids can selectively target specific proteins. One family of lipid-regulated membrane proteins is the TWIK-related K channel (TREK) subfamily of K2P channels: TREK1, TREK2, and TWIK-related arachdonic acid stimulated K(+) channel (TRAAK). We investigated the regulation of TREK channels by phosphatidic acid (PA), which is generated by phospholipase D (PLD) via hydrolysis of phosphatidylcholine. Even though all three of the channels are sensitive to PA, we found that only TREK1 and TREK2 are potentiated by PLD2 and that none of these channels is modulated by PLD1, indicating surprising selectivity. We found that PLD2, but not PLD1, directly binds to the C terminus of TREK1 and TREK2, but not to TRAAK. The results have led to a model for selective lipid regulation by localization of phospholipid enzymes to specific effector proteins. Finally, we show that regulation of TREK channels by PLD2 occurs natively in hippocampal neurons.

publication date

  • September 16, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4169921

Digital Object Identifier (DOI)

  • 10.1073/pnas.1407160111

PubMed ID

  • 25197053

Additional Document Info

start page

  • 13547

end page

  • 52

volume

  • 111

number

  • 37