Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.

The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β 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 pep...

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Autores principales:	Margaret H Magdesian, Matthias Gralle, Luiz H Guerreiro, Paulo José I Beltrão, Milena M V F Carvalho, Luís Eduardo da S Santos, Fernando G de Mello, Ricardo A M Reis, Sérgio T Ferreira
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f79b5e71009f43b2a9cfc8411a12416d
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spelling	oai:doaj.org-article:f79b5e71009f43b2a9cfc8411a12416d2021-11-18T06:49:01ZSecreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.1932-620310.1371/journal.pone.0022857https://doaj.org/article/f79b5e71009f43b2a9cfc8411a12416d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829538/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β 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 sAPPα(695) (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 sAPPα(695) binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPα(695) inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (K(d)≤8·10(-9) M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPα 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 sAPPα modulates the biological action of semaphorins.Margaret H MagdesianMatthias GralleLuiz H GuerreiroPaulo José I BeltrãoMilena M V F CarvalhoLuís Eduardo da S SantosFernando G de MelloRicardo A M ReisSérgio T FerreiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22857 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margaret H Magdesian Matthias Gralle Luiz H Guerreiro Paulo José I Beltrão Milena M V F Carvalho Luís Eduardo da S Santos Fernando G de Mello Ricardo A M Reis Sérgio T Ferreira Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
description	The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β 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 sAPPα(695) (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 sAPPα(695) binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPα(695) inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (K(d)≤8·10(-9) M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPα 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 sAPPα modulates the biological action of semaphorins.
format	article
author	Margaret H Magdesian Matthias Gralle Luiz H Guerreiro Paulo José I Beltrão Milena M V F Carvalho Luís Eduardo da S Santos Fernando G de Mello Ricardo A M Reis Sérgio T Ferreira
author_facet	Margaret H Magdesian Matthias Gralle Luiz H Guerreiro Paulo José I Beltrão Milena M V F Carvalho Luís Eduardo da S Santos Fernando G de Mello Ricardo A M Reis Sérgio T Ferreira
author_sort	Margaret H Magdesian
title	Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
title_short	Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
title_full	Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
title_fullStr	Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
title_full_unstemmed	Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
title_sort	secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f79b5e71009f43b2a9cfc8411a12416d
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Secreted human amyloid precursor protein binds semaphorin 3a and prevents semaphorin-induced growth cone collapse.

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