PT  - JOURNAL ARTICLE
AU  - E. Nicholas Petersen
AU  - Manasa Gudheti
AU  - Mahmud Arif Pavel
AU  - Keith R. Murphy
AU  - William W. Ja
AU  - Erik M. Jorgensen
AU  - Scott B. Hansen
TI  - Phospholipase D Transduces Force to TREK-1 Channels in a Biological Membrane
AID  - 10.1101/758896
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 758896
4099  - http://biorxiv.org/content/early/2019/09/05/758896.short
4100  - http://biorxiv.org/content/early/2019/09/05/758896.full
AB  - The transduction of force into a biological signal is critical to all living organisms. Recently, disruption of ordered lipids has emerged as an ‘atypical’ force sensor in biological membranes; however, disruption has yet to link with canonical channel mechanosensation. Here we show that forceinduced disruption and lipid mixing activates TWIK-related K+ channel (TREK-1), and that this activation is dependent on phospholipase D2 (PLD2). PLD2 transduces the force into a chemical signal phosphatidic acid (PA) that is then sensed by TREK-1 with a latency of <3 ms. TREK-1 then produces a mechanically induced change in membrane potential. Hence, in a biological membrane, we show the ordered lipid is the force sensor, PLD2 is a chemical transducer, and the ‘mechanosensitive’ ion channel TREK-1 is a downstream effector of mechanical transduction. Confirming this central role for PA singling in force transduction, genetic deletion of PLD decreases mechanosensitivity and pain thresholds in D. melanogaster.