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Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse (2011)
BibTeX
@MISC{Magdesian11secretedhuman,
author = {Margaret H. Magdesian and Matthias Gralle and Luiz H. Guerreiro and Paulo José and I. Beltrão and Milena M. V. F and Luís Eduardo and S. Santos and O G. De Mello and Ricardo A. M. Reis and Sérgio T. Ferreira},
title = {Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse},
year = {2011}
}
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Abstract
The amyloid precursor protein (APP) is well known for giving rise to the amyloid-b peptide and for its role in Alzheimer’s disease. Much less is known, however, on the physiological roles of APP in the development and plasticity of the central nervous system. We have used phage display of a peptide library to identify high-affinity ligands of purified recombinant human sAPPa695 (the soluble, secreted ectodomain from the main neuronal APP isoform). Two peptides thus selected exhibited significant homologies with the conserved extracellular domain of several members of the semaphorin (Sema) family of axon guidance proteins. We show that sAPPa695 binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPa 695 inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (K d#8?10 29 M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPa binding and its inhibitory action on Sema3A function. These two peptides are comprised within a domain previously shown to be involved in binding of Sema3A to its cellular receptor, suggesting a competitive mechanism by which sAPPa modulates the biological action of
Keyphrases
prevents semaphorin-induced growth cone collapse phage display embryonic chicken purified recombinant human sappa695 amyloid precursor protein transfected hek293 cell main neuronal app isoform dorsal root ganglion growth cone sappa binding competitive mechanism alzheimer disease purified recombinant sema3a exhibited significant homology sema3a-derived peptide central nervous system conserved extracellular domain amyloid-b peptide several member peptide library sema3a function biological action physiological role high-affinity ligand axon guidance protein inhibitory action cellular receptor
