Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling

Author:

Moehring Francie1ORCID,Cowie Ashley M1,Menzel Anthony D1,Weyer Andy D1,Grzybowski Michael2,Arzua Thiago2,Geurts Aron M2,Palygin Oleg2ORCID,Stucky Cheryl L1ORCID

Affiliation:

1. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States

2. Department of Physiology, Medical College of Wisconsin, Milwaukee, United States

Abstract

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.

Funder

National Institute of Neurological Disorders and Stroke

Medical College of Wisconsin

Marvin Wagner Endowed Professorship

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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