Swedish Nerve Growth Factor Mutation (NGFR100W ) Defines a Role for TrkA and p75NTR in Nociception

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Kijung SungChengbiao Wu

Abstract

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGFβ sequence (NGFR100W) in patients with hereditary sensory and autonomic neuropathy type V (HSAN V) made it possible to distinguish the signaling mechanisms that lead to two functionally different outcomes of NGF: trophic versus nociceptive. We performed extensive biochemical, cellular, and live-imaging experiments to examine the binding and signaling properties of NGFR100W Our results show that, similar to the wild-type NGF (wtNGF), the naturally occurring NGFR100W mutant was capable of binding to and activating the TrkA receptor and its downstream signaling pathways to support neuronal survival and differentiation. However, NGFR100W failed to bind and stimulate the 75 kDa neurotrophic factor receptor (p75NTR)-mediated signaling cascades (i.e., the RhoA-Cofilin pathway). Intraplantar injection of NGFR100W into adult rats induced neither TrkA-mediated thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia based on agonism for TrkA signaling. Together, our studies provide evi...Continue Reading

Citations

Feb 28, 2019·PloS One·Kayla SheehanMark Schumacher
May 15, 2020·The Prostate·Zhiqiang LiuPraveen Thumbikat
Jun 20, 2020·Translational Neurodegeneration·Ruinan ShenChengbiao Wu
May 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Giovanna TestaSimona Capsoni

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