| First Author | Chasseigneaux S | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 1 | Pages | e16301 |
| PubMed ID | 21298006 | Mgi Jnum | J:223709 |
| Mgi Id | MGI:5660096 | Doi | 10.1371/journal.pone.0016301 |
| Citation | Chasseigneaux S, et al. (2011) Secreted amyloid precursor protein beta and secreted amyloid precursor protein alpha induce axon outgrowth in vitro through Egr1 signaling pathway. PLoS One 6(1):e16301 |
| abstractText | BACKGROUND: sAPPalpha released after alpha secretase cleavage of Amyloid Precursor Protein (APP) has several functions including the stimulation of neurite outgrowth although detailed morphometric analysis has not been done. Two domains involved in this function have been described and are present in sAPPbeta released at the first step of amyloid peptide cleavage, raising the possibility that sAPPbeta could also stimulate neurite outgrowth. We investigated the morphological effects of sAPPalpha and sAPPbeta on primary neurons and identified a key signaling event required for the changes observed. METHODOLOGY/PRINCIPAL FINDINGS: Final concentrations of 50 to 150 nM bacterial recombinant sAPPalpha or sAPPbeta added to primary neuronal cultures after 1 day in vitro decreased cell adhesion 24 hours later and primary dendrite length 96 hours later. 150 nM sAPPalpha and sAPPbeta induced a similar increase of axon outgrowth, although this increase was already significant at 100 nM sAPPalpha. These morphological changes induced by sAPPs were also observed when added to differentiated neurons at 5 days in vitro. Real time PCR and immunocytochemistry showed that sAPPalpha and sAPPbeta stimulated Egr1 expression downstream of MAPK/ERK activation. Furthermore, in primary neurons from Egr1 -/- mice, sAPPs affected dendritic length but did not induce any increase of axon length. CONCLUSION/SIGNIFICANCE: sAPPalpha and sAPPbeta decrease cell adhesion and increase axon elongation. These morphological changes are similar to what has been observed in response to heparan sulfate. The sAPPalpha/sAPPbeta stimulated increase in axon growth requires Egr1 signaling. These data suggest that sAPPbeta is not deleterious per se. Since sAPPbeta and sAPPalpha are present in the embryonic brain, these two APP metabolites might play a role in axon outgrowth during development and in response to brain damage. |
