Optical Control of Endogenous Proteins with a Photoswitchable Conditional Subunit Reveals a Role for TREK1 in GABAB Signaling Academic Article uri icon

Overview

MeSH Major

  • Neurons
  • Potassium Channels, Tandem Pore Domain
  • Receptors, GABA-B
  • Signal Transduction

abstract

  • Selective ligands are lacking for many neuronal signaling proteins. Photoswitched tethered ligands (PTLs) have enabled fast and reversible control of specific proteins containing a PTL anchoring site and have been used to remote control overexpressed proteins. We report here a scheme for optical remote control of native proteins usingĀ a "photoswitchable conditional subunit" (PCS), which contains the PTL anchoring site as well as a mutation that prevents it from reaching the plasma membrane. In cells lacking native subunits for the protein, the PCS remains nonfunctional internally. However, in cells expressing native subunits, the native subunit and PCS coassemble, traffic to the plasma membrane, and place the native protein under optical control provided by the coassembled PCS. We apply this approach to the TREK1 potassium channel, which lacks selective, reversible blockers. We find that TREK1, typically considered to be a leak channel, contributes to the hippocampal GABA(B) response.

publication date

  • June 21, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3383668

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2012.04.026

PubMed ID

  • 22726831

Additional Document Info

start page

  • 1005

end page

  • 14

volume

  • 74

number

  • 6