Aβ impairs the LTP-related movement of endogenous CaMKII but not of exogenous GFP-CaMKII.

Abstract

Amyloid β (Aβ) inhibits hippocampal long-term potentiation (LTP; a form of synaptic plasticity thought to underly learning and memory) by inhibiting the stimulation-induced synaptic accumulation of the Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII). Notably, CaMKII inhibition rescues both CaMKII movement and LTP, indicating that CaMKII mediates both LTP and the Aβ-induced LTP impairment. Somewhat counterintuitively, we found here that overexpression of GFP-CaMKII also rescued the Aβ-induced impairment of CaMKII movement. For endogenous CaMKII, we confirmed that Aβ indeed induced impairment of movement, and that previous results with live-imaging approaches were not due to Aβ-induced dissociation of the CaMKII intrabody. For exogenous GFP-CaMKII, the effect did not depend on the expression level and was thus likely caused by the N-terminal GFP label. Surprisingly, placing the GFP label instead at the C-terminus (near the association domain) still allowed CaMKII holoenzyme formation and still protected from the Aβ-induced impairment of CaMKII movement. Thus, while our method allows replacing endogenous CaMKII with similar amounts of GFP-CaMKII, our results provide a rare example for GFP-CaMKII not recapitulating the function of endogenous CaMKII.