Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways

Tools

Item Type:	Article
Title:	Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways
Creators Name:	Simonetti, M., Agarwal, N., Stösser, S., Bali, K.K., Karaulanov, E., Kamble, R., Pospisilova, B., Kurejova, M., Birchmeier, W., Niehrs, C., Heppenstall, P. and Kuner, R.
Abstract:	Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we report that Wnt signaling pathways persist in adult sensory neurons and play a functional role in their sensitization in a pathophysiological context. We observed that Wnt3a recruits the Wnt-calcium signaling pathway and the Wnt planar cell polarity pathway in peripheral nerves to alter pain sensitivity in a modality-specific manner and we elucidated underlying mechanisms. In contrast, biochemical, pharmacological, and genetic studies revealed lack of functional relevance for the classical canonical {beta}-catenin pathway in peripheral sensory neurons in acute modulation of nociception. Finally, this study provides proof-of-concept for a translational potential for Wnt3a-Frizzled3 signaling in alleviating disease-related pain hypersensitivity in cancer-associated pain in vivo.
Keywords:	Cultured Cells, Frizzled Receptors, HEK293 Cells, Hyperalgesia, Peripheral Nerves, Sensory Receptor Cells, Spinal Ganglia, Wnt Signaling Pathway, Wnt3A Protein, Animals, Mice
Source:	Neuron
ISSN:	0896-6273
Publisher:	Cell Press
Volume:	83
Number:	1
Page Range:	104-121
Date:	2 July 2014
Official Publication:	https://doi.org/10.1016/j.neuron.2014.05.037
PubMed:	View item in PubMed

Repository Staff Only: item control page