Your browser doesn't support javascript.
loading
Secreted Amyloid Precursor Protein-Alpha Enhances LTP Through the Synthesis and Trafficking of Ca2+-Permeable AMPA Receptors.
Livingstone, Rhys W; Elder, Megan K; Singh, Anurag; Westlake, Courteney M; Tate, Warren P; Abraham, Wickliffe C; Williams, Joanna M.
Afiliación
  • Livingstone RW; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Elder MK; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Singh A; Department of Psychology, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Westlake CM; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Tate WP; Department of Biochemistry, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Abraham WC; Department of Psychology, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Williams JM; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
Front Mol Neurosci ; 14: 660208, 2021.
Article en En | MEDLINE | ID: mdl-33867938
Regulation of AMPA receptor expression by neuronal activity and neuromodulators is critical to the expression of both long-term potentiation (LTP) and memory. In particular, Ca2+-permeable AMPARs (CP-AMPAR) play a unique role in these processes due to their transient, activity-regulated expression at synapses. Secreted amyloid precursor protein-alpha (sAPPα), a metabolite of the parent amyloid precursor protein (APP) has been previously shown to enhance hippocampal LTP as well as memory formation in both normal animals and in Alzheimer's disease models. In earlier work we showed that sAPPα promotes trafficking of GluA1-containing AMPARs to the cell surface and specifically enhances synthesis of GluA1. To date it is not known whether de novo synthesized GluA1 form CP-AMPARs or how they contribute to sAPPα-mediated plasticity. Here, using fluorescent non-canonical amino acid tagging-proximity ligation assay (FUNCAT-PLA), we show that brief treatment of primary rat hippocampal neurons with sAPPα (1 nM, 30 min) rapidly enhanced the cell-surface expression of de novo GluA1 homomers and reduced levels of de novo GluA2, as well as extant GluA2/3-AMPARs. The de novo GluA1-containing AMPARs were localized to extrasynaptic sites and later internalized by sAPPα-driven expression of the activity-regulated cytoskeletal-associated protein, Arc. Interestingly, longer exposure to sAPPα increased synaptic levels of GluA1/2 AMPARs. Moreover, the sAPPα-mediated enhancement of LTP in area CA1 of acute hippocampal slices was dependent on CP-AMPARs. Together, these findings show that sAPPα engages mechanisms which specifically enhance the synthesis and cell-surface expression of GluA1 homomers, underpinning the sAPPα-driven enhancement of synaptic plasticity in the hippocampus.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Mol Neurosci Año: 2021 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Mol Neurosci Año: 2021 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza