Margaret Stratton, PhD
Assistant Professor
Department of Biochemistry and Molecular Biology
University of Massachusetts, Amherst
(October 12, 2017)
Activation-Triggered Subunit Exchange in CaMKII and Its Role in Memory
Memory formation, storage, and retrieval is a long-term process, and requires a cellular component, such as a protein, that can remain active over long periods of time. This has been an open question for many years, as most proteins degrade over time. Doctor Stratton’s research has demonstrated that CaMKII can produce long-term activation by the sharing of subunits (molecular components of the protein) with other CaMKII proteins. Doctor Stratton has determined that this sharing is activity-dependent. In this way, it is thought that CaMKII is in control of the persistent activity needed for memory formation.
Memories are stored and retrieved over a time-scale of decades while cellular components are degraded on a time-scale of minutes to days. Addressing this significant discrepancy is what drives the Stratton lab’s research. It was more than two decades ago that Francis Crick speculated that perhaps an oligomeric protein could solve this degradation paradox. He postulated that this oligomer could serve as a molecular memory by sharing its activation state with newly synthesized proteins through subunit exchange. John Lisman later suggested that Ca2+-calmodulin dependent protein kinase II (CaMKII) is a good candidate for this ‘memory protein’. Stratton’s lab has recently shown, for the first time, that subunit exchange does occur between CaMKII holoenzymes. Importantly, this occurs only as a result of activation, and activation (phosphorylation in this case) is spread as a consequence of subunit exchange. This would be a mundane result if subunit exchange were not activation-dependent, since all protein oligomers disassemble and reassemble at some rate. It is exciting that there is something unique about the CaMKII assembly that allows this regulation. Long-term potentiation (LTP) requires persistent activity to sustain synaptic signaling over a long period of time (how long exactly remains unclear). She hypothesized that subunit exchange in CaMKII may be the key to this persistent activation.