Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 27, Issue 4, Pages 379-393Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2004.08.001
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- NIA NIH HHS [1 P50 AG16582] Funding Source: Medline
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Neuregulin-l (NRG-1) growth and differentiation factors and their erbB receptors are hypothesized to promote embryonic hippocampal neuron differentiation via as yet unknown mechanisms. We have found that NRG-1beta increases the outgrowth of primary neurites, neuronal area, total neurite length, and neuritic branching in E18 hippocampal neurons. NRG-1beta effects on neurite extension and arborization are similar to, but not additive with, those of brain-derived neurotrophic factor and reflect direct NRG-1 action on hippocampal neurons as these cells express the NRG-1 receptors erbB2 and erbB4, the erbB-specific inhibitor PD1158780 decreases NRG-10 induced neurite outgrowth, and NRG-1beta stimulation induces p42/44 ERK phosphorylation. Pharmacological inhibition of p42/44 ERK and protein kinase C (PKC), but not PI3K or p38 MAP kinase, inhibits NRG-1beta-induced neurite extension and elaboration. We conclude that NRG-1beta stimulates hippocampal neurite extension and arborization via a signaling pathway that involves erbB membrane tyrosine kinases (erbB2 and/or erbB4), p42/44 ERK, and PKC. (C) 2004 Elsevier Inc. All rights reserved.
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