Figure 8
From: Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway
Schematic model for regulation of Nav1.6 by APP.
APP through VTPEER activates Go protein, which enhances phosphorylation of APP (Thr668) by activating of JNK3. Phosphorylated APP (Thr668) binds to Nav1.6 and promotes cell surface expression of Nav1.6. In addition, activation of Goα further enhances the functional interaction between phosphorylated APP (Thr668) and Nav1.6. AICD, after cleavage from full-length APP, upon being phosphylated (Thr668), increases cell surface expression of Nav1.6 as well, which is also mediated by activity of Goα. Phosphorylated APP/AICD (Thr668) mediates cell surface expression of Nav1.6 may through promoting Nav1.6 insert into the cell surface or maintaining Nav1.6 on the cell surface.
