Study Shows Detailed Molecular Workings of a Key System in Learning and Memory Formation

One of the new realities in biomedical research is that it’s increasingly difficult to use a general approach to score advances. Now, investigations into disease mechanisms, for example, are often conducted at the molecular level by specialists who dedicate years to interrogating a single protein or signaling pathway.

One such scientist is biochemist Margaret Stratton (M2M), whose lab reports how they used advanced sequencing technology to clear up uncertainty and determine all variants of a single protein/enzyme known as calcium/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus, the brain’s memory center.

It plays a central role in calcium signaling throughout the body, Stratton explains. In the hippocampus, CaMKII is required for learning and memory, and when mutations occur they contribute to conditions such as autism spectrum disorders and developmental disabilities, or problems in other systems relating to cardiac pacing and fertility.

Stratton and first authors Roman Sloutsky and Noelle Dziedzic, with others, report in Science Signaling that they found an unexpected new role for the hub domain, or organizational center of the CaMKII molecular complex. Stratton says, “In addition to this known role, we show that this domain affects how sensitive CaMKII is to calcium; it acts like a tuner for sensitivity. This was a surprise. It opens a whole new area for investigation. We also show evidence for how we think it works at the molecular level.”