English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha

MPS-Authors
/persons/resource/persons208051

Kochen,  Lisa
Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society;

/persons/resource/persons207927

tom Dieck,  Susanne
Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society;

/persons/resource/persons208206

Schuman,  Erin
Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Mockett, B. G., Guèvremont, D., Elder, M. K., Parfitt, K. D., Peppercorn, K., Morrissey, J., et al. (2019). Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha. The Journal of Neuroscience, 39(17), 3188-3203. doi:10.1523/JNEUROSCI.1826-18.2019.


Cite as: http://hdl.handle.net/21.11116/0000-0007-A8A2-4
Abstract
Secreted amyloid precursor protein-alpha (sAPP) has growth factor-like properties and can modulate long-term potentiation (LTP)and memory. Here, we demonstrate that exposure to sAPPconverts short-lasting LTP into protein-synthesis-dependent late LTP inhippocampalslicesfrommalerats.sAPPhadnodiscernableeffect.WehypothesizedthatsAPPfacilitatedLTPviaregulatedglutamatereceptor trafficking anddenovoprotein synthesis. We found using a linear mixed model that sAPPstimulated trafficking of GluA2-lacking AMPARs, as well as NMDARs to the extrasynaptic cell surface, in a calcium/calmodulin-dependent kinase II and protein kinaseG-dependent manner. Both cell surface receptor accumulation and LTP facilitation were present even after sAPPwashout and inhibi-tion ofreceptor trafficking or protein synthesis prevented all these effects. Direct visualization of newly synthesized proteins (FUNCAT-PLA)confirmed the ability of sAPPto stimulatedenovoprotein synthesis and revealed GluA1 as one of the upregulated proteins. Therefore, sAPPgenerates a coordinated synthesis and trafficking of glutamate receptors to the cell surface that facilitate LTP