Fine-tuned protein makes memoriesby Leigh MacMillan Jun. 24, 2011, 2:42 PM
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 “scaffolding” protein that assembles multiprotein complexes at sites of neuronal signaling.
Roger Colbran 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’s 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 research was supported by the National Institute of Mental Health, the American Heart Association, and the UNCF Merck Science Initiative.