Schwann cell-sensory neuron complex and sensory mechanotransduction

Abstract

The recent discovery of nociceptive Schwann cells has changed our vision of how mechanotransduction occurs in sensory neurons. We have described a diversity of sensory Schwann cells that participate on mechanotransduction in mechanoreceptors and nociceptors. Here, we have demonstrated that Sox10+ Schwann cells display mechanosensitive currents by indentation. Optogenetic manipulation of Sox10+ Schwann cells in Meissner corpuscles as in A-fiber and C-fiber mechanonociceptors demonstrated that these cells influence the mechanical threshold, sensitivity and adaptation of cutaneous sensory neurons. Particularly, sensory Schwann cells in Meissner corpuscles are compartamelized and influence different aspects of Aβ-fibers excitability. Sox10+ Schwann cells are tightly coupled with sensory afferent terminal endings and participate in mechanosensitivity and AP initiation, while Sox2+ are associated with excitability and adaption properties. Similar functional structure has been found in hair follicles innervated by Aβ-fibers and associated with Sox2+ Schwann cells. In nociceptors, Sox10+ Schwann cells seem to be directly coupled to the terminal endings and influence their mechanical threshold and adaption properties. Thus, the sensory Schwann cell and terminal endings of cutaneous sensory neurons are a diverse and conserved feature in specialized receptors for mechanotransduction. The TMEM150C/Ttn3 transmembrane protein was recently proposed as a mechanosensitive ion channel. Here we have overexpressed TMEM150C/Ttn3 in naïve cells and stimulated with mechanical indentation, no mechanosensitive currents were observed or modulation of mechanically gated ion channels such as Piezo2. Additionally, we have used the ex vivo skin-nerve preparation to characterize the role of TMEM150C/Ttn3 in cutaneous sensory neurons function in two mutant mice where the gene was ablated. The TMEM150CLacZ/LacZ mouse line was generated by introducing a LacZ and neomycin cassette and disrupt the allele is expected. Skin nerve preparation recordings and mousewalk behavior test showed no difference between wild-type and knockout mice. However, it is possible that DRG neurons go through alternative splicing and part of the gene generates a truncated protein. The TMEM150C-/- mouse was generated using CRISPR/Cas technology where the N-terminal sequence of the allele is deleted, and no transcripts are produced. Preliminary results suggest that TMEM150C seem to participate in slowly adapting properties of mechanoreceptors and nociceptors.