TY - JOUR TI - Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling AU - Moehring, Francie AU - Cowie, Ashley M AU - Menzel, Anthony D AU - Weyer, Andy D AU - Grzybowski, Michael AU - Arzua, Thiago AU - Geurts, Aron M AU - Palygin, Oleg AU - Stucky, Cheryl L A2 - Ginty, David D VL - 7 PY - 2018 DA - 2018/01/16 SP - e31684 C1 - eLife 2018;7:e31684 DO - 10.7554/eLife.31684 UR - https://doi.org/10.7554/eLife.31684 AB - The first point of our body’s contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions. KW - tactile KW - epidermis KW - optogenetics KW - cell sniff KW - purinoceptors KW - mechanotransduction JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -