Glutamate Receptor Trafficking and Protein Synthesis Mediate the Facilitation of LTP by Secreted Amyloid Precursor Protein-Alpha

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Bruce G MockettWickliffe C Abraham

Abstract

Secreted amyloid precursor protein-alpha (sAPPα) has growth factor-like properties and can modulate long-term potentiation (LTP) and memory. Here, we demonstrate that exposure to sAPPα converts short-lasting LTP into protein-synthesis-dependent late LTP in hippocampal slices from male rats. sAPPβ had no discernable effect. We hypothesized that sAPPα facilitated LTP via regulated glutamate receptor trafficking and de novo protein synthesis. We found using a linear mixed model that sAPPα stimulated trafficking of GluA2-lacking AMPARs, as well as NMDARs to the extrasynaptic cell surface, in a calcium/calmodulin-dependent kinase II and protein kinase G-dependent manner. Both cell surface receptor accumulation and LTP facilitation were present even after sAPPα washout and inhibition of receptor trafficking or protein synthesis prevented all these effects. Direct visualization of newly synthesized proteins (FUNCAT-PLA) confirmed the ability of sAPPα to stimulate de novo protein synthesis and revealed GluA1 as one of the upregulated proteins. Therefore, sAPPα generates a coordinated synthesis and trafficking of glutamate receptors to the cell surface that facilitate LTP.SIGNIFICANCE STATEMENT Secreted amyloid precursor protein-alpha (...Continue Reading

Citations

Oct 4, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Danielle K Bailey, Daniel J Kosman
Sep 3, 2019·Frontiers in Molecular Neuroscience·Rhys W LivingstoneJoanna M Williams
Oct 15, 2019·Frontiers in Aging Neuroscience·Laura García-GonzálezSantiago Rivera
Jan 25, 2020·Nucleic Acids Research·Bella KoltunKobi Rosenblum
Nov 5, 2019·Frontiers in Cellular Neuroscience·Jodi A MorrisseyWickliffe C Abraham
Apr 20, 2021·Frontiers in Molecular Neuroscience·Rhys W LivingstoneJoanna M Williams
Jun 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Susann LudewigMartin Korte
Jul 27, 2021·Seminars in Cell & Developmental Biology·Mauricio M Oliveira, Eric Klann
Sep 22, 2021·Life Science Alliance·Karen ArnaudAriel A Di Nardo

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