Amyloid Precursor Protein Knockout Diminishes Synaptic Vesicle Proteins at the Presynaptic Active Zone in Mouse Brain
2014
The amyloid precursor protein (APP) has previously been allocated to an organellar pool residing in the Golgi
apparatus and in endosomal compartments, and in its mature form to a presynaptic active zone-localized pool. By analyzing
homozygous APP knockout mice we evaluated the impact of APP on synaptic vesicle protein abundance at synaptic
release sites. Following immunopurification of synaptic vesicles and the attached presynaptic plasma membrane, individual
proteins were subjected to quantitative Western blot analysis. We demonstrate that APP deletion in knockout animals
reduces the abundance of the synaptic vesicle proteins synaptophysin, synaptotagmin-1, and SV2A at the presynaptic active
zone. Conversely, deletion of the additional APP family members, APLP1 and APLP2 resulted in an increase in synaptophysin,
synaptogamin-1, and SV2A abundance. When transmembrane APP is lacking in APPsα-KI/APLP2-KO mice
synaptic vesicle protein abundance corresponds to that in APP -KO mice. Deletion of the synaptic vesicle protein 2 (SV2)
A and B had no effect on APP and synaptophysin abundance but decreased synaptotagmin-1. Our data suggest that APP
controls the abundance of synaptic vesicle proteins at the presynaptic release sites and thus impacts synaptic transmission.
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