This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers at the Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University, Kyoto University, SOKENDAI and the National Institute for Physiological Sciences have revealed how CaMKIIα—a key brain protein involved in learning and memory—organizes itself into chain-like structures. Their study, published in Science Advances, shows how activation causes these protein structures to grow and how a mutation associated with neurodevelopmental disorders changes their organization, findings that could deepen our understanding of memory formation and neurological disease.
As new memories form, connections between brain cells can become stronger. A protein called CaMKIIα plays an important part in this process and is found in especially large amounts at the points where brain cells communicate. Scientists have long known that more of this protein gathers at active connections, but they have not been able to see clearly how the individual protein molecules come together.
In the new study, a team led by Mikihiro Shibata used high-speed atomic force microscopy, a technique that can visualize individual molecules at very high resolution, to observe how CaMKIIα molecules move and interact in real time. The researchers discovered that, under crowded conditions similar to those inside brain-cell connections, the molecules join together to form chain-like structures. CaMKIIα normally assembles as a ring-shaped complex called a holoenzyme, typically containing 12 protein subunits.
At low concentrations, where the holoenzymes could diffuse freely, more than 95% appeared as individual particles, whether inactive or activated. Stable clusters did not form. The picture changed when the researchers recreated two important features of the postsynaptic environment: high molecular density and restricted movement.
Under these spatially confined conditions, CaMKIIα holoenzymes contacted one another and assembled into stable chains containing several holoenzymes. The contact points observed by HS-AFM indicated that the interactions occurred through the proteins' kinase domains—the regions responsible for catalytic activity. The clusters began to form at densities below those estimated within the postsynaptic density, the protein-rich signaling region of a synapse.
This suggests that the crowded and constrained environment of a dendritic spine could strongly favor higher-order CaMKIIα organization. When calcium levels rise inside a brain cell, another molecule called calmodulin switches on CaMKIIα. This causes the working parts of the protein, known as kinase domains, to move outward.
Extract — continue reading at the source.
