Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL.
Bottom Line: 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.APRIL promoted phosphorylation and activation of ERK1, ERK2 and Akt and serine phosphorylation and inactivation of GSK-3β in cultured hippocampal pyramidal cells.
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.