Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling. Elife 2018 Jan 16;7
Date
01/18/2018Pubmed ID
29336303Pubmed Central ID
PMC5777822DOI
10.7554/eLife.31684Scopus ID
2-s2.0-85042135972 (requires institutional sign-in at Scopus site) 149 CitationsAbstract
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.
Author List
Moehring F, Cowie AM, Menzel AD, Weyer AD, Grzybowski M, Arzua T, Geurts AM, Palygin O, Stucky CLAuthors
Aron Geurts PhD Professor in the Physiology department at Medical College of WisconsinCheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Cells, Cultured
Humans
Keratinocytes
Mice, Inbred C57BL
Mice, Knockout
Optogenetics
Receptors, Purinergic P2X4
Signal Transduction
Touch
