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Developmental switch in NF-kappa B signalling required for neurite growth

Gavalda, Nuria, Gutierrez, Humberto ORCID: and Davies, Alun M. ORCID: 2009. Developmental switch in NF-kappa B signalling required for neurite growth. Development 136 (20) , pp. 3405-3412. 10.1242/dev.035295

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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-κB 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-κB activation mechanism and the phosphorylation status of the p65 NF-κB subunit required for neurite growth. Shortly before birth, BDNF activates NF-κB by an atypical mechanism that involves tyrosine phosphorylation of IκBα by Src family kinases, and dephosphorylates p65 at serine 536. Immediately after birth, BDNF-independent constitutive activation of NF-κB signalling by serine phosphorylation of IκBα and constitutive dephosphorylation of p65 at serine 536 are required for BDNF-promoted neurite growth. This abrupt developmental switch in NF-κB 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Uncontrolled Keywords: NF-κB; Neurite growth; Signalling; BDNF; Sensory neuron
Publisher: The Company of Biologists Ltd
ISSN: 0950-1991
Funders: Wellcome Trust
Last Modified: 17 Oct 2022 10:38

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