淀粉样前体蛋白敲除减少小鼠突触前活跃区域的突触蘘泡蛋白

Title:Amyloid Precursor Protein Knockout Diminishes Synaptic Vesicle Proteins at the Presynaptic Active Zone in Mouse Brain

Volume: 11 Issue: 10

Author(s): Melanie Laßek, Jens Weingarten, Amparo Acker-Palmer, Sandra M. Bajjalieh, Ulrike Muller and Walter Volknandt

Affiliation:

关键词: 淀粉样前体蛋白APP，APLP1，APLP2，停驻突触蘘泡，突触前活跃区域，SV2，突触结合蛋白-1，突触小泡。

摘要: 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.

Cite this article as:

Melanie Laßek, Jens Weingarten, Amparo Acker-Palmer , Sandra M. Bajjalieh, Ulrike Muller and Volknandt Walter, Amyloid Precursor Protein Knockout Diminishes Synaptic Vesicle Proteins at the Presynaptic Active Zone in Mouse Brain, Current Alzheimer Research 2014; 11 (10) . https://dx.doi.org/10.2174/1567205011666141107152458