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Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts
Author(s) -
Talagas Matthieu,
Lebonvallet Nicolas,
Leschiera Raphael,
Sinquin Gerard,
Elies Philippe,
Haftek Marek,
Pennec JeanPierre,
Ressnikoff Denis,
La Padula Veronica,
Le Garrec Raphaele,
L'herondelle Killian,
Mignen Olivier,
Le Pottier Laetitia,
Kerfant Nathalie,
Reux Alexia,
Marcorelles Pascale,
Misery Laurent
Publication year - 2020
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25912
Subject(s) - sensory system , neuroscience , free nerve ending , transduction (biophysics) , synaptic vesicle , biology , sensory neuron , anatomy , vesicle , biochemistry , genetics , membrane
Objective Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons. Methods Contacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies. Results Epidermal keratinocytes dialogue with sensory neurons through en passant synaptic‐like contacts. These contacts have the ultrastructural features and molecular hallmarks of chemical synaptic‐like contacts: narrow intercellular cleft, keratinocyte synaptic vesicles expressing synaptophysin and synaptotagmin 1, and sensory information transmitted from keratinocytes to sensory neurons through SNARE‐mediated (syntaxin1) vesicle release. Interpretation By providing selective communication between keratinocytes and sensory neurons, synaptic‐like contacts are the hubs of a 2‐site receptor. The permanent epidermal turnover, implying a specific en passant structure and high plasticity, may have delayed their identification, thereby contributing to the long‐held concept of nerve endings passing freely between keratinocytes. The discovery of keratinocyte–sensory neuron synaptic‐like contacts may call for a reassessment of basic assumptions in cutaneous sensory perception and sheds new light on the pathophysiology of pain and itch as well as the physiology of touch. ANN NEUROL 2020;88:1205–1219