Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons.
Neuregulin-1 (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 PD158780 decreases NRG-1beta 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.
Gerecke
Kimberly M
KM
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Wyss
J Michael
JM
Carroll
Steven L
SL
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D020890:Neuregulin-1; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000494:pharmacology / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020033:Protein Isoforms; D011493:Protein Kinase C; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C490580:Nrg1 protein, rat; C587691:Erbb4 protein, rat