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Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL

Osório, Catarina Raquel, Chacon Fernandez, Pedro J., White, Matthew, Kisiswa, Lilian, Wyatt, Sean Lee, Rodríguez-Tébar, Alfredo and Davies, Alun M. 2014. Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL. Molecular and Cellular Neuroscience 59 , pp. 24-36. 10.1016/j.mcn.2014.01.002

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Abstract

APRIL (A Proliferation-Inducing Ligand, TNFSF13) is a member of the tumor necrosis factor superfamily that regulates lymphocyte survival and activation and has been implicated in tumorigenesis and autoimmune diseases. Here we report the expression and first known activity of APRIL in the nervous system. APRIL and one of its receptors, BCMA (B-Cell Maturation Antigen, TNFRSF17), are expressed by hippocampal pyramidal cells of fetal and postnatal mice. In culture, these neurons secreted APRIL, and function-blocking antibodies to either APRIL or BCMA reduced axonal elongation. Recombinant APRIL enhanced axonal elongation, but did not influence dendrite elongation. The effect of APRIL on axon elongation was inhibited by anti-BCMA and the expression of a signaling-defective BCMA mutant in these neurons, suggesting that the axon growth-promoting effect of APRIL is mediated by BCMA. APRIL promoted phosphorylation and activation of ERK1, ERK2 and Akt and serine phosphorylation and inactivation of GSK-3β in cultured hippocampal pyramidal cells. Inhibition of MEK1/MEK2 (activators of ERK1/ERK2), PI3-kinase (activator of Akt) or Akt inhibited the axon growth-promoting action of APRIL, as did pharmacological activation of GSK-3β and the expression of a constitutively active form of GSK-3β. These findings suggest that APRIL promotes axon elongation by a mechanism that depends both on ERK signaling and PI3-kinase/Akt/GSK-3β signaling.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Hippocampal pyramidal cell; Axon; Tumor necrosis factor superfamily; Tumor necrosis factor receptor superfamily
Publisher: Elsevier
ISSN: 1044-7431
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 10 January 2014
Last Modified: 28 Jun 2019 02:01
URI: http://orca.cf.ac.uk/id/eprint/58109

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