FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation
| Autor: | Paul Strecker, Marco B. Rust, Suzanne Y. Guénette, Tabea A. Mundinger, Christina Mehrfeld, Elisa G. Krächan, Martin Korte, Andreas Görlich, Stefan Kins, Joachim Herz, Susann Ludewig |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Dendritic spine Genotype Dendritic Spines Long-Term Potentiation Neuromuscular Junction Hippocampus Nerve Tissue Proteins Anxiety Motor Activity Models Biological Neuromuscular junction Article 03 medical and health sciences Amyloid beta-Protein Precursor 0302 clinical medicine Postsynaptic potential Amyloid precursor protein medicine Animals Learning APLP1 Maze Learning APLP2 Adaptor Proteins Signal Transducing Mice Knockout Memory Disorders Multidisciplinary biology Pyramidal Cells Nuclear Proteins Long-term potentiation Epistasis Genetic Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Synapses biology.protein Carrier Proteins Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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