Developmental switch in NF-kappaB signalling required for neurite growth.
For a given cell type, particular extracellular signals generate characteristic patterns of activity in intracellular signalling networks that lead to distinctive cell-type specific responses. Here, we report the first known occurrence of a developmental switch in the intracellular signalling network required for an identical cellular response to the same extracellular signal in the same cell type. We show that although NF-kappaB signalling is required for BDNF-promoted neurite growth from both foetal and postnatal mouse sensory neurons, there is a developmental switch between these stages in the NF-kappaB activation mechanism and the phosphorylation status of the p65 NF-kappaB subunit required for neurite growth. Shortly before birth, BDNF activates NF-kappaB by an atypical mechanism that involves tyrosine phosphorylation of IkappaBalpha by Src family kinases, and dephosphorylates p65 at serine 536. Immediately after birth, BDNF-independent constitutive activation of NF-kappaB signalling by serine phosphorylation of IkappaBalpha and constitutive dephosphorylation of p65 at serine 536 are required for BDNF-promoted neurite growth. This abrupt developmental switch in NF-kappaB signalling in a highly differentiated cell type illustrates an unsuspected plasticity in signalling networks in the generation of identical cellular responses to the same extracellular signal.
Gavaldà
Núria
N
Cardiff School of Biosciences, Biomedical Building, Wales, UK.
Gutierrez
Humberto
H
Davies
Alun M
AM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D016328:NF-kappa B; D010768:Phosphoserine; D019000:Phosphotyrosine; D019061:src-Family Kinases; D051550:I-kappa B Kinase