Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse
| العنوان: | Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse |
|---|---|
| المؤلفون: | Margaret H. Magdesian, Milena M. V. F. Carvalho, Luiz Henrique Guerreiro, Paulo José I. Beltrão, Fernando G. de Mello, Luis E. Santos, Ricardo Augusto de Melo Reis, Sergio T. Ferreira, Matthias Gralle |
| المصدر: | PLoS ONE PLoS ONE, Vol 6, Iss 7, p e22857 (2011) |
| بيانات النشر: | Public Library of Science, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Gene isoform, Phage display, animal structures, Protein Conformation, Science, Growth Cones, Peptide, Chick Embryo, Biology, Kidney, Signaling Pathways, Amyloid beta-Protein Precursor, Semaphorin, Developmental Neuroscience, Peptide Library, Ganglia, Spinal, Amyloid precursor protein, Animals, Humans, Immunoprecipitation, Peptide library, Cells, Cultured, chemistry.chemical_classification, Multidisciplinary, Neuronal Morphology, SEMA3A, Semaphorin-3A, Molecular biology, Peptide Fragments, Cell biology, Axon Guidance, chemistry, Ectodomain, Cellular Neuroscience, Culture Media, Conditioned, biology.protein, Medicine, Molecular Neuroscience, Research Article, Neuroscience |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d950d1b54106c7f2322b500bb247a7bbTest http://europepmc.org/articles/PMC3146505Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d950d1b54106c7f2322b500bb247a7bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|