The enzyme CaMKII is a central player in the neuronal signaling that builds memories. Precise control of CaMKII activity depends on proteins such as densin, a 鈥渟caffolding鈥� protein that assembles multiprotein complexes at sites of neuronal signaling.
and colleagues have discovered new features of the CaMKII-densin interaction. They report in the Journal of Biological Chemistry that densin can interact with multiple CaMKII types in mouse brain and cultured cells.
They identified a novel binding site for CaMKII in an internal region of the densin protein and found that this densin-IN domain is 50 percent similar to a known CaMKII inhibitor protein. The densin-IN domain and the full densin protein inhibited CaMKII鈥檚 ability to phosphorylate, or modify, one type of excitatory glutamate receptor, AMPA, but not another type, NMDA. The findings suggest a unique mechanism for fine-tuning CaMKII activity toward different targets, which could play a role in the synaptic plasticity that underlies learning and memory.
The was supported by the National Institute of Mental Health, the American Heart Association, and the UNCF Merck Science Initiative.