FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation

• Verfasst von: Strecker, Paul [VerfasserIn]
• Verfasst von: Mundinger, Tabea Anne [VerfasserIn]
• Verfasst von: Kins, Stefan [VerfasserIn]
• Titel: FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation
• Verf.angabe: Paul Strecker, Susann Ludewig, Marco Rust, Tabea A. Mundinger, Andreas Görlich, Elisa G. Krächan, Christina Mehrfeld, Joachim Herz, Martin Korte, Suzanne Y. Guénette & Stefan Kins
• E-Jahr: 2016
• Jahr: 11 May 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 19.05.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2016
• Band/Heft Quelle: 6(2016) Artikel-Nummer 25652, 13 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/srep25652
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698558120

Abstract

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.