Editors' ChoiceSensory Perception

Pinpointing the Pressure Responder

Science Signaling  03 Jun 2014:
Vol. 7, Issue 328, pp. ec148
DOI: 10.1126/scisignal.2005544

Touch perception is complex because both pressure and tactile features, such as ridges and edges, must be distinguished. Merkel cells are specialized epidermal cells of the epithelial lineage that exhibit properties of sensory receptor cells and that function with slowly adapting type 1 (SA1) afferent neurons in the perception of touch. A pair of papers used genetic knockout experiments and optogenetic techniques to demonstrate that Merkel cells have a mechanosensory transduction function mediated by Piezo2 channels and that these cells contribute specific information about touch to the afferent neurons. Maksimovic et al. used mice that expressed green fluorescent protein (GFP) in Merkel cells to isolate these cells. Currents from isolated Merkel cells exhibited properties resembling those of mechanosensitive channels and the mRNA for Piezo2, a cation-permeable mechanosensitive channel, was enriched in these cells. Selective expression of light-regulated activating or inhibiting channels (using optogenetic techniques) to either stimulate or inhibit Merkel cell function in intact skin showed that these cells stimulated SA1 afferents and were necessary for the static, prolonged portion of SA1 responses, not the initial high-frequency SA1 responses. Mice genetically deficient in Merkel cells exhibited not only loss of the sustained response to touch but also a reduction in the dynamic firing necessary for tactile exploration and interpretation of texture. Woo et al. explored the function of Piezo2 in touch perception. Consistent with the mRNA data from Maksimovic et al., Woo et al. showed that a GFP reporter for the Piezo2 gene was expressed only in Merkel cells in the skin. Mice engineered with skin-specific Piezo2 knockout exhibited morphologically normal Merkel cell-neurite complexes and had normal abundance of Piezo2 mRNA in dorsal root ganglion neurons. Isolated GFP-expressing Merkel cells from Piezo2-deficient mice did not respond to mechanical stimuli that produced a rapidly adapting current in GFP-expressing Merkel cells from control mice. (Merkel cells in both the control and Piezo2-deficient mice expressed GFP to facilitate isolation.) Ex vivo skin preparations showed that firing of the SA1 afferents in response to touch was lower in Piezo2-deficient mice than in wild-type mice. Furthermore, electrophysiological characterization showed that Piezo2 in Merkel cells was required for sustained firing throughout the duration of the stimulation and that the SA1 afferents in Piezo2-deficient skin preparations exhibited an intermediately adapting firing pattern instead of a slowly adapting firing pattern. Consistent with a deficit in light touch, the Piezo2-deficient mice were less responsive to low-force mechanical stimuli. Together, these studies demonstrate that the Merkel cell is a functional mechanosensory cell and is required for passing specific information about mechanical stimuli to the afferent nerve.

S. Maksimovic, M. Nakatani, Y. Baba, A. M. Nelson, K. L. Marshall, S. A. Wellnitz, P. Firozi, S.-H. Woo, S. Ranade, A. Patapoutian, E. A. Lumpkin, Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509, 617–621 (2014). [PubMed]

S.-H. Woo, S. Ranade, A. D. Weyer, A. E. Dubin, Y. Baba, Z. Qiu, M. Petrus, T. Miyamoto, K. Reddy, E. A. Lumpkin, C. L. Stucky, A. Patapoutian, Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622–626 (2014). [PubMed]