Identification of a Novel Signaling Pathway and Its Relevance for GluA1 Recycling

We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3) increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation of PI(3,5)P2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5)P2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory

Seebohm and Husserl on the Humanities

This essay discusses Husserl’s brief and Seebohm’s much more extensive comments on the grounding of several disciplines commonly described under the heading of “the humanities” as sciences in his History as a Science and the System of the Sciences. It asks not just what Husserl and Seebohm say about the grounding of these disciplines as empirical sciences, but also whether we can understand what they have to say by applying what they have to say to the actual practice of these disciplines, thereby extending and refining some of the rather general claims they make about the way they should and do proceed as genuine sciences in the sense indicated above. It does not attempt to do this with all of the humanities but with a few paradigmatic examples, all of which, as academic disciplines, typically take texts and the matters these texts are directed to as the objects of their studies. It thereby becomes clear in the summary of Husserl’s and Seebohm’s positions on the grounding of the Geisteswissenschaften (Husserl’s term, not Seebohm’s) why the notion of interpretation is so important, in particular for literary studies and history, but not so much for applied disciplines such as composition studies or foreign language instruction that are part of humanities departments but do not fit the classic model of the Geisteswissenschaften as theoretical, interpretive disciplines