Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL.
Bottom Line: 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.
Affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AT Wales, United Kingdom.Show MeSH
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Mentions: Glycogen synthase kinase-3 (GSK-3) proteins are among the many substrates of Akt kinases, and have been implicated in the regulation of multiple aspects of neural development (Hur and Zhou, 2010), including the control of axon growth from developing sensory and hippocampal neurons (Kim et al., 2006; Zhou et al., 2004). The two isoforms of GSK-3, GSK-3α and GSK-3β, can be phosphorylated on serine-21 and serine-9, respectively, by Akt kinases (Cross et al., 1995). This results in inactivation of GSK-3, and several studies suggest that inactivated GSK-3 promotes axon elongation from cultured sensory and hippocampal neurons by regulating the molecular machinery that controls actin rearrangement and microtubule assembly (Kim et al., 2006; Kumar et al., 2009; Namekata et al., 2012; Yoshimura et al., 2005; Zhou et al., 2004). To determine if treating hippocampal neurons with APRIL leads to GSK-3 phosphorylation, we cultured E18 pyramidal cells for 3 days before treating them with APRIL. Western blot analysis revealed that APRIL caused a rapid increase in the phosphorylation of phospho-S9 GSK-3β that was sustained for at least 60 min (Fig. 8A and B), but caused no change in the level of phospho-S21 GSK-3α.
Affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AT Wales, United Kingdom.