期刊
NEURON
卷 74, 期 6, 页码 1005-1014出版社
CELL PRESS
DOI: 10.1016/j.neuron.2012.04.026
关键词
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资金
- National Institutes of Health [PN2EY018241, R01 NS35549]
- National Science Foundation [FIBR 0623527]
- Chateaubriand Fellowship Program
- Philippe Foundation
- French National Center for Scientific Research (CNRS)
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 using 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.
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