Adjunct Assistant Professor of Chemistry and Biochemistry

Office: Natural Sciences Bldg
Phone:
Email: nakagawa@ucsd.edu
Web: nakagawalab.ucsd.edu 
Group: View group members

2007-2011

John Merck Scholarship

2007

Hellman Faculty Fellow

2003-2005

HHMI Postdoctoral Fellow

2001-2005

Massachusetts Institute of Technology

2000-2003

Human Frontier Science Program Long-Term Fellow

2000-2001

Massachusetts General Hospital, Harvard Medical School

Molecular mechanism of synaptic plasticity.

Neurons in the brain form neural circuits by making contact with each other at the structures known as synapses. In many cases, electrical signals are converted to chemical signals at the synapses and transmitted from one neuron to another through the mechanisms of synaptic transmission. At the synapse, protein complexes formed of ion channels and soluble signaling proteins function in regulating synaptic transmission. My laboratory is interested in understanding the changes of these macromolecular machineries (i.e. changes in composition, conformation, and modification) in response to neuronal activity. Our primary focus will be on glutamate receptors and their macromolecular assembly formed of scaffold proteins. We combine techniques in molecular and cellular methods, biochemistry, and imaging to accomplish the task. Studying the mechanisms of synaptic function is likely to tell us more about the normal physiology and pathology of the nervous system at the molecular level.

Projects

(1) Understanding the structural basis of AMPA receptor function using cryo-EM

Development of a purification method to isolate intact AMPA receptors from the brain allows us to study the structural basis for the function of these important ligand gated ion channels in the synapse. Based on the 35 Angstrom density map we published in 2005 and 2006, we are currently working on to obtain higher resolution structure of the intact tetrameric AMPA receptors using cryo electron microscopy. We expect to understand the accurate subunit arrangements within the tetrameric AMPA receptors and further obtain clues to the glutamate induced conformational changes.

(2) Molecular mechanism of the functional modulation of AMPA receptors by stargazin/TARP

Modulation of AMPA receptors affects synaptic plasticity at the cellular level and influences cognition at the level of behavior. Membrane proteins in the stargazin/TARP family are auxiliary subunits of native AMPA receptors in the brain and modulate ion channel functioning by slowing down the desensitization kinetics. Using electron microscopy and electrophysiological recordings, we intend to further identify the mechanism of the modulation of AMPA receptors by stargazin/TARP.

(3) Determining the modular organization of the synaptic plasticity machinery

Through the approaches taken by molecular cloning and protein identification through mass spectrometry, neuroscientists have the overall view about the variety of the molecules (mainly proteins) that exists in the synapse. It remains less known how these proteins assemble and exert their functions during synaptic plasticity. On the assumption that modular organization of macromolecules forms the basis of synaptic structure and function, we intend to isolate and characterize novel protein complexes involved in synaptic plasticity. By accumulating the information on the variety and function of macromolecular machinery in the synapse, we intend to provide an explanation for the modular organization of the synapse.

Macromolecular Structure
Biophysics
Cellular Biochemistry