Journal article

Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF

Adrianna Kalous, Matthew R Nangle, Agustin Anastasia, Barbara L Hempstead, Janet R Keast

JOURNAL OF NEUROCHEMISTRY | WILEY-BLACKWELL | Published : 2012

Abstract

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 obser..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Institutes of Health


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (Senior Research Fellowships #570877 and 632903 to J.R.K), the New South Wales (NSW) Office for Science and Medical Research "Spinal Cord Injury and Other Neurological Conditions'' Program Grant (J.R.K), National Institutes of Health (NS 30687 to B.L.H.) and Australian Postgraduate Award (to A.K). Current affiliation of A.K.: Department of Physiology, Development & Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. AK, MN, AA and JK participated in conducting the experimental work. All authors contributed to conception and design of the study, analysis or interpretation of the data and writing the manuscript. The authors have no conflicts of interest to declare.