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FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation
The FE65 adaptor proteins (FE65, FE65L1 and FE65L2) bind proteins that function in diverse cellular pathways and are essential for specific biological processes. Mice lacking both FE65 and FE65L1 exhibit ectopic neuronal positioning in the cortex and muscle weakness. p97FE65-KO mice, expressing a sh...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899880/ https://www.ncbi.nlm.nih.gov/pubmed/27734846 http://dx.doi.org/10.1038/srep25652 |
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author | Strecker, Paul Ludewig, Susann Rust, Marco Mundinger, Tabea A. Görlich, Andreas Krächan, Elisa G. Mehrfeld, Christina Herz, Joachim Korte, Martin Guénette, Suzanne Y. Kins, Stefan |
author_facet | Strecker, Paul Ludewig, Susann Rust, Marco Mundinger, Tabea A. Görlich, Andreas Krächan, Elisa G. Mehrfeld, Christina Herz, Joachim Korte, Martin Guénette, Suzanne Y. Kins, Stefan |
author_sort | Strecker, Paul |
collection | PubMed |
description | The FE65 adaptor proteins (FE65, FE65L1 and FE65L2) bind proteins that function in diverse cellular pathways and are essential for specific biological processes. Mice lacking both FE65 and FE65L1 exhibit ectopic neuronal positioning in the cortex and muscle weakness. p97FE65-KO mice, expressing a shorter FE65 isoform able to bind amyloid precursor protein family members (APP, APLP1, APLP2), develop defective long-term potentiation (LTP) and aged mice display spatial learning and memory deficits that are absent from young mice. Here, we examined the central and peripheral nervous systems of FE65-KO, FE65L1-KO and FE65/FE65L1-DKO mice. We find spatial learning and memory deficits in FE65-KO and FE65L1-KO mice. Severe motor impairments, anxiety, hippocampal LTP deficits and neuromuscular junction (NMJ) abnormalities, characterized by decreased size and reduced apposition of pre- and postsynaptic sites, are observed in FE65/FE65L1-DKO mice. As their NMJ deficits resemble those of mutant APP/APLP2-DKO mice lacking the FE65/FE65L1 binding site, the NMJs of APLP2/FE65-DKO and APLP2/FE65L1-DKO mice were analyzed. NMJ deficits are aggravated in these mice when compared to single FE65- and FE65L1-KO mice. Together, our data demonstrate a role for FE65 proteins at central and peripheral synapses possibly occurring downstream of cell surface-associated APP/APLPs. |
format | Online Article Text |
id | pubmed-4899880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48998802016-06-13 FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation Strecker, Paul Ludewig, Susann Rust, Marco Mundinger, Tabea A. Görlich, Andreas Krächan, Elisa G. Mehrfeld, Christina Herz, Joachim Korte, Martin Guénette, Suzanne Y. Kins, Stefan Sci Rep Article The FE65 adaptor proteins (FE65, FE65L1 and FE65L2) bind proteins that function in diverse cellular pathways and are essential for specific biological processes. Mice lacking both FE65 and FE65L1 exhibit ectopic neuronal positioning in the cortex and muscle weakness. p97FE65-KO mice, expressing a shorter FE65 isoform able to bind amyloid precursor protein family members (APP, APLP1, APLP2), develop defective long-term potentiation (LTP) and aged mice display spatial learning and memory deficits that are absent from young mice. Here, we examined the central and peripheral nervous systems of FE65-KO, FE65L1-KO and FE65/FE65L1-DKO mice. We find spatial learning and memory deficits in FE65-KO and FE65L1-KO mice. Severe motor impairments, anxiety, hippocampal LTP deficits and neuromuscular junction (NMJ) abnormalities, characterized by decreased size and reduced apposition of pre- and postsynaptic sites, are observed in FE65/FE65L1-DKO mice. As their NMJ deficits resemble those of mutant APP/APLP2-DKO mice lacking the FE65/FE65L1 binding site, the NMJs of APLP2/FE65-DKO and APLP2/FE65L1-DKO mice were analyzed. NMJ deficits are aggravated in these mice when compared to single FE65- and FE65L1-KO mice. Together, our data demonstrate a role for FE65 proteins at central and peripheral synapses possibly occurring downstream of cell surface-associated APP/APLPs. Nature Publishing Group 2016-05-11 /pmc/articles/PMC4899880/ /pubmed/27734846 http://dx.doi.org/10.1038/srep25652 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Strecker, Paul Ludewig, Susann Rust, Marco Mundinger, Tabea A. Görlich, Andreas Krächan, Elisa G. Mehrfeld, Christina Herz, Joachim Korte, Martin Guénette, Suzanne Y. Kins, Stefan FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title | FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title_full | FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title_fullStr | FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title_full_unstemmed | FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title_short | FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation |
title_sort | fe65 and fe65l1 share common synaptic functions and genetically interact with the app family in neuromuscular junction formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899880/ https://www.ncbi.nlm.nih.gov/pubmed/27734846 http://dx.doi.org/10.1038/srep25652 |
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