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Disruption of palmitate-mediated localization; a shared pathway of force and anesthetic activation of TREK-1 channels
| Content Provider | Scilit |
|---|---|
| Author | Petersen, E. Nicholas Pavel, Mahmud Arif Wang, Hao Hansen, Scott B. |
| Copyright Year | 2019 |
| Description | Journal: Biochimica Et Biophysica Acta (bba) - Biomembranes TWIK related K+ channel (TREK-1) is a mechano- and anesthetic sensitive channel that when activated attenuates pain and causes anesthesia. Recently the enzyme phospholipase D2 (PLD2) was shown to bind to the channel and generate a local high concentration of phosphatidic acid (PA), an anionic signaling lipid that gates TREK-1. In a biological membrane, the cell harnesses lipid heterogeneity (lipid compartments) to control gating of TREK-1 using palmitate-mediated localization of PLD2. Here we discuss the ability of mechanical force and anesthetics to disrupt palmitate-mediated localization of PLD2 giving rise to TREK-1's mechano- and anesthetic-sensitive properties. The likely consequences of this indirect lipid-based mechanism of activation are discussed in terms of a putative model for excitatory and inhibitory mechano-effectors and anesthetic sensitive ion channels in a biological context. Lastly, we discuss the ability of locally generated PA to reach mM concentrations near TREK-1 and the biophysics of localized signaling. Palmitate-mediated localization of PLD2 emerges as a central control mechanism of TREK-1 responding to mechanical force and anesthetic action. This article is part of a Special Issue entitled: Molecular biophysics of membranes and membrane proteins. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907892/pdf |
| Ending Page | 183091 |
| Page Count | 1 |
| Starting Page | 183091 |
| ISSN | 00052736 |
| DOI | 10.1016/j.bbamem.2019.183091 |
| Journal | Biochimica Et Biophysica Acta (bba) - Biomembranes |
| Issue Number | 1 |
| Volume Number | 1862 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-10-28 |
| Access Restriction | Open |
| Subject Keyword | Journal: Biochimica Et Biophysica Acta (bba) - Biomembranes Super Resolution Microscopy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Biophysics |
