Amyloid precursor protein knockout diminishes synaptic vesicle proteins at the presynaptic active zone in mouse brain.
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.
Melanie
M
Laßek
Jens
J
Weingarten
Amparo
A
Acker-Palmer
Sandra M
SM
Bajjalieh
Ulrike
U
Muller
Department of Molecular and Cellular Neurobiology, Biologicum, Goethe-University, Max-von-Laue-Str. 13, 60438 Frankfurt/Main, Germany. volknandt@bio.uni-frankfurt.de.
Walter
W
Volknandt
D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050863:Synaptotagmin I / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; C492952:Aplp2 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489614:Sv2a protein, mouse; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse