Figure 6.

Hypothetical mechanism for the role of APP and PS in the stabilization of KARs at Mf–CA3 synapses. A, Representative scheme of a synaptic site with Mf–CA3 synapses in control conditions. APP is expressed at presynaptic and postsynaptic sites and acts as a transmembrane adhesion protein. We hypothesize that APP interacts with Neto1, an auxiliary subunit of KARs present at Mf–CA3 synapses, therefore providing a mechanism for anchoring KARs at these synaptic sites. KARs are likely to be recruited and stabilized by additional mechanisms (including N-cadherins or C1ql2). B, In the absence of APP from postsynaptic CA3 pyramidal cells, KARs may loose its anchor to transsynaptic adhesion molecules and be destabilized from synapses. Extrasynaptic KARs are sent to degradation pathways. C, In the absence of PS from postsynaptic CA3 pyramidal cells, there is an accumulation of the APP βCTF, which competes for the interaction of APP with the Neto1/KAR complex, which in turn destabilizes KARs from synapses.