TY - JOUR TI - Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons AU - Narayanan, Pratibha AU - Hütte, Meike AU - Kudryasheva, Galina AU - Taberner, Francisco J AU - Lechner, Stefan G AU - Rehfeldt, Florian AU - Gomez-Varela, David AU - Schmidt, Manuela A2 - Bassereau, Patricia VL - 7 PY - 2018 DA - 2018/03/09 SP - e32346 C1 - eLife 2018;7:e32346 DO - 10.7554/eLife.32346 UR - https://doi.org/10.7554/eLife.32346 AB - Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2. Experiments with catalytically inactive Mtmr2, pharmacological blockers of PI(3,5)P2 synthesis, and osmotic stress suggest that Mtmr2-dependent Piezo2 inhibition involves depletion of PI(3,5)P2. Further, we identified a PI(3,5)P2 binding region in Piezo2, but not Piezo1, that confers sensitivity to Mtmr2 as indicated by functional analysis of a domain-swapped Piezo2 mutant. Altogether, our results propose local PI(3,5)P2 modulation via Mtmr2 in the vicinity of Piezo2 as a novel mechanism to dynamically control Piezo2-dependent mechanotransduction in peripheral sensory neurons. KW - Piezo2 KW - PI(3,5)P2 KW - Mtmr2 KW - mechanotransduction KW - somatosensation KW - peripheral sensory nerves JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -