Margaret Stratton
Assistant Professor
Office
LGRT 1226
(413) 545-0631
Fax
(413) 545-3291
Focus
understanding, at the molecular level, the proteins that are involved in long-term memory formation
Background and Training

PhD: SUNY Upstate Medical University

Postdoctoral training: University of California, Berkeley

Research Summary

https://sites.biochem.umass.edu/strattonlab/

The Stratton Lab will focus on the study of CaMKII in three major areas: frequency activation, subunit exchange, and downstream effectors. The overarching goal of the Stratton lab is to understand, at the molecular level, the proteins that are involved in long-term memory formation. In order to understand the complexity that exists in our neural networks, we first need a detailed understanding of the proteins involved in memory formation at the level of their molecular structure, signaling properties and regulation. We aim to bridge the gap between information obtained at the animal level (e.g., transgenic mice) and information obtained at the molecular level (e.g., protein structure and regulation).

Ca2+-calmodulin dependent protein kinase II (CaMKII) is a crucial molecular component of long-term memory formation. Interestingly, this dodecameric enzyme responds to the frequency, and not just the amplitude, of Ca2+ spikes and this property is important for its role in long-term potentiation (LTP). Neuronal communication is facilitated through pulse frequency, and high frequency pulses over a significant duration lead to LTP. We will characterize CaMKII in terms of its frequency response as well as the structural determinants of its signaling properties and regulation.

CaMKII exchanges subunits between holoenzymes in an activation-dependent manner. This phenomenon may lend CaMKII the ability to spread activation so that it outlasts protein degradation rates and, importantly, provide a persistent signal that could potentiate memory at the molecular level. The Stratton lab will continue to study subunit exchange in CaMKII, as well as downstream targets of CaMKII and the effects of these signaling processes on memory formation. We will focus on biochemical and biophysical techniques, complemented by in cellulo experiments and microscopy, to demonstrate the physiological relevance of these phenomena.

Publications

1)   M. M. Stratton*, I. H. Lee*, M. Bhattacharyya, S. M. Christensen, L. H. Chao, H. Schulman, J. T. Groves, J. Kuriyan, (2014) Activation-triggered subunit exchange between CaMKII holoenzymes facilitates the spread of kinase activity, eLife3:e01610. [PubMed]

2)   M. M. Stratton, L. H. Chao, H. Schulman, J. Kuriyan, (2013) Structural studies on the regulation of Ca2+/calmodulin dependent protein kinase II, Current opinion in structural biology23, 292-301. [PubMed]

3)   L. H. Chao, M. M. Stratton, I. H. Lee, J. Levitz, D. Mandell, T. Kortemme, H. Schulman, J. Kuriyan, (2011) A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin- dependent kinase II holoenzyme, Cell146, 732-745. [PubMed]

4)   M. M. Stratton*, S. McClendon*, D. Eliezer, and S. N. Loh, (2011), Structural characterization of two alternate conformations in a Calbindin D9k-based molecular switch, Biochemistry50, 5583-5589[PubMed]

5)   M. M. Stratton and S. N. Loh, (2011) Converting a protein into a switch for biosensing and functional regulation, Protein Science20, 19-29. [PubMed]

6)   M. M. Stratton and S.N. Loh, (2010) On the mechanism of protein fold-switching by a molecular sensor,Proteins,78, 3260-3269. [PubMed]

7)   M. M. Stratton, T. A. Cutler, J. H. Ha, and S. N. Loh, (2010), Probing local structural fluctuations in myoglobin by size-dependent thiol-disulfide exchange, Protein Science, 19,1587-1594[PubMed]

8)   M. M. Stratton, D. M. Mitrea and S. N. Loh, (2008) A Ca2+-sensing molecular switch based on alternate frame protein folding, ACS Chem. Biol.3, 723-732. [PubMed]