ALBERT

Description: The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380172/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ranade, Sanjeev S -- Woo, Seung-Hyun -- Dubin, Adrienne E -- Moshourab, Rabih A -- Wetzel, Christiane -- Petrus, Matt -- Mathur, Jayanti -- Begay, Valerie -- Coste, Bertrand -- Mainquist, James -- Wilson, A J -- Francisco, Allain G -- Reddy, Kritika -- Qiu, Zhaozhu -- Wood, John N -- Lewin, Gary R -- Patapoutian, Ardem -- 101054/Wellcome Trust/United Kingdom -- R01 DE022358/DE/NIDCR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 4;516(7529):121-5. doi: 10.1038/nature13980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Department of Neuroscience, Max-Delbruck Center for Molecular Medicine, Robert-Rossle Strasse 10, D-13092 Berlin, Germany [2] Klinik fur Anasthesiologie mit Schwerpunkt Operative Intensivmedizin, Campus Charite Mitte and Virchow-Klinikum Charite, Universitatsmedizin Berlin, Augustburgerplatz 1, 13353 Berlin, Germany. ; Department of Neuroscience, Max-Delbruck Center for Molecular Medicine, Robert-Rossle Strasse 10, D-13092 Berlin, Germany. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; 1] Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA [2] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25471886" target="_blank"〉PubMed〈/a〉