Toshi Kawate
Assistant Professor

Toshi Kawate

Phone

607-253-3783

Address

Department of Molecular Medicine
C4-151 Veterninary Medical Center
Cornell University
Ithaca, NY 14583

Email

Web Sites

Department Profile
Lab Website

Background

Toshi is interested in how proteins are built and how they drive complex biological systems. A graduate from Osaka University, he received his Ph.D. in Cellular, Molecular, and Biophysical Studies at Columbia University, where he established his research background in X-ray crystallography and protein biochemistry in the lab of Dr. Eric Gouaux. He continued his postdoctoral research in the lab of Dr. Kenton Swartz at the NIH where he learned ion channel biophysics and electrophysiology. Toshi became an Assistant Professor at the Department of Molecular Medicine at Cornell University in the summer of 2011.

Research Description

Our lab is particularly interested in the mechanisms of membrane proteins involved in extracellular adenosine-5'-triphosphate (ATP) mediated signaling. While ATP is a pivotal molecule in all living organisms, providing energy required for metabolism, biosynthesis, and intracellular signaling, this versatile molecule also plays critical roles as a signal transmitter in cell-cell communication. In the nervous system, for example, ATP is released from neurons or glial cells through different mechanisms such as exocytosis, through membrane channels, or through ruptured membranes of dying cells. Released ATP molecules are recognized by two different classes of ATP-receptors: i) ionotropic P2X receptors, and ii) G-protein coupled P2Y receptors. Binding of ATP to P2 receptors initiates Ca2+ mediated signaling, evokes action potentials in post-synaptic neurons, or propagates Ca2+ waves through astrocytes. Knock-down studies and pharmacological experiments have shown that P2 receptors serve important functions in diverse physiological systems, ranging from sensation of taste and pain to inflammation initiation and T-cell activation. What are the molecular mechanisms of ATP-recognition and the subsequent transduction of signals? We are trying to elucidate these mechanisms by using a combination of x-ray crystallographic, biophysical and biochemical techniques, and electrophysiological methods. The knowledge we gain may in turn lead to new approaches for controlling pain and alleviating inflammatory diseases, such as arthritis and asthma.

Publications

Kawate T*, Robertson JL, Li M, Silberberg SD, and Swartz KJ*. (2011) Ion access pathway to the transmembrane pore in P2X receptor channels. J Gen Physiol 137:579-90 *co-corresponding authors

Li M, Kawate T, Silberberg SD, and Swartz KJ. (2010) Pore-opening mechanism in trimeric P2X receptor channels. Nat Commun 1:44

Kawate T, Carlisle Michel J, Birdsong WT, and Gouaux E. (2009) Crystal structure of the ATP-gated P2X4 ion channel in the closed state. Nature 460:592-8

Gonzales EB, Kawate T, and Gouaux E. (2009) Pore architecture and ion sites in acid sensing ion channels and P2X receptors. Nature 460:599-604

Kawate T and Gouaux E. (2006) Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. Structure14:673-681

Yamashita A, Singh SK, Kawate T, Jin Y, and Gouaux E. (2005) Crystal structure of a bacterial homologue of Na+/Cl- dependent neurotransmitter transporters. Nature 437:215-23

Takeda T, Kawate T, and Chang F. (2004) Organization of a sterol-rich membrane domain by cdc15p during cytokinesis in fission yeast. Nat Cell Biol 6:1142-4

Sineshchekova OO, Kawate T, Vdovychenko OV, and Sato TN. (2004) Protein-trap version 2.1: screening for expressed proteins in mammalian cells based on their localizations. BMC Cell Biology 02;5:8

Kawate T and Gouaux E. (2003) Arresting and releasing Staphylococcal α-hemolysin at intermediate stages of pore formation by engineered disulfide bonds. Protein Science 12:997-1006