Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF
Article first published online: 12 JUN 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 122, Issue 3, pages 523–536, August 2012
How to Cite
Kalous, A., Nangle, M. R., Anastasia, A., Hempstead, B. L. and Keast, J. R. (2012), Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF. Journal of Neurochemistry, 122: 523–536. doi: 10.1111/j.1471-4159.2012.07799.x
- Issue published online: 9 JUL 2012
- Article first published online: 12 JUN 2012
- Accepted manuscript online: 23 MAY 2012 09:31AM EST
- Received November 3, 2011; revised manuscript received April 15, 2012; accepted May 15, 2012.
- dorsal root ganglion;
- satellite cells;
J. Neurochem. (2012) 122, 523–536.
The nerve growth factor (NGF) precursor, proNGF, is implicated in various neuropathological states. ProNGF signals apoptosis by forming a complex with the receptors p75 and sortilin, however, it can also induce neurite growth, proposed to be mediated by the receptor of mature NGF, tyrosine kinase receptor A (TrkA). The way in which these dual effects occur in adult neurons is unclear. We investigated the neurotrophic effects of proNGF on peptidergic sensory neurons isolated from adult mouse dorsal root ganglia and found that proNGF stimulated neurite extension and branching, requiring p75, sortilin and TrkA. Neurite growth rarely occurred in sortilin-expressing neurons but was commonly observed in TrkA-positive, sortilin-negative neurons that associated closely with sortilin-positive glia. ProNGF was unable to induce local trophic effects at growth cones where sortilin-positive glia was absent. We propose that in adult sensory neurons the neurotrophic response to proNGF is mediated by NGF and TrkA, and that peri-somatic glia may participate in sortilin- and p-75 dependent cleavage of proNGF. The potential ability of local glial cells to provide a targeted supply of NGF may provide an important way to promote trophic (rather than apoptotic) outcomes under conditions where regeneration or sprouting is required.