The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function.
Processing of Aβ-precursor protein (APP) plays an important role in Alzheimer's Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3062548?pdf=render |
| _version_ | 1818298615097982976 |
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| author | Alessia P M Barbagallo Zilai Wang Hui Zheng Luciano D'Adamio Luciano D'Adamio |
| author_facet | Alessia P M Barbagallo Zilai Wang Hui Zheng Luciano D'Adamio Luciano D'Adamio |
| author_sort | Alessia P M Barbagallo |
| collection | DOAJ |
| description | Processing of Aβ-precursor protein (APP) plays an important role in Alzheimer's Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis.To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr(668) is replaced by an Ala (T(668)A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T(668)A allele into the APLP2 knockout background showed that mutation of Thr(668) does not cause a defective phenotype. Notably, the T(668)A mutant APP is able to bind Mint1.Our results argue against an important role of the Thr(668) residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved in those APP-mediated functions that prevent (NMJ) defects and early lethality in APLP2 null mice. |
| first_indexed | 2024-12-13T04:38:08Z |
| format | Article |
| id | doaj.art-8674f38349d34e26b0d2d82e88161f85 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:38:08Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8674f38349d34e26b0d2d82e88161f852022-12-21T23:59:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1800610.1371/journal.pone.0018006The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function.Alessia P M BarbagalloZilai WangHui ZhengLuciano D'AdamioLuciano D'AdamioProcessing of Aβ-precursor protein (APP) plays an important role in Alzheimer's Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis.To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr(668) is replaced by an Ala (T(668)A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T(668)A allele into the APLP2 knockout background showed that mutation of Thr(668) does not cause a defective phenotype. Notably, the T(668)A mutant APP is able to bind Mint1.Our results argue against an important role of the Thr(668) residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved in those APP-mediated functions that prevent (NMJ) defects and early lethality in APLP2 null mice.http://europepmc.org/articles/PMC3062548?pdf=render |
| spellingShingle | Alessia P M Barbagallo Zilai Wang Hui Zheng Luciano D'Adamio Luciano D'Adamio The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. PLoS ONE |
| title | The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. |
| title_full | The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. |
| title_fullStr | The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. |
| title_full_unstemmed | The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. |
| title_short | The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function. |
| title_sort | intracellular threonine of amyloid precursor protein that is essential for docking of pin1 is dispensable for developmental function |
| url | http://europepmc.org/articles/PMC3062548?pdf=render |
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