A hyperglycosylated form of Kv1.2 upregulated in LGI1 knockout mice

Abstract

Kv1 voltage-gated potassium channels determine key functional neuronal properties. Their activity is modulated by subunit composition and post-translational modifications such as phosphorylation and glycosylation. Using an antibody directed against a phosphotyrosine (Y458) located in the C-terminal tail of Kv1.2, we identified yet unreported high molecular weight forms of Kv1.2 among them, a phosphorylated and heavily glycosylated 100 kDa form. Owing to the significant downregulation of Kv1.2 in LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, we investigated, in total brain and the hippocampal formation of both WT and Lgi1-/- mice, the distribution of phosphoY458 Kv1.2 and we compared their respective proteomic interactomes with those of Kv1.2. In addition to major differences between the interactomes of pY458Kv1.2 and Kv1.2 in WT and Lgi1-/-, we found a major reshaping of pY458 Kv1.2 molecular neighbourhood between WT and Lgi1-/- as well as a significant upregulation of the glycosylated form in Lgi1-/-.