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Research

Background

Every single cell possesses a cytoplasmic membrane which consists of a phospholipid bilayer. The membrane covers the cell surface and distinguish the inside and outside of the cell. In addition, the inside of cell is divided into several compartments by biological membranes. These membranes restrict transports of molecules between inside and outside of cells or cellular compartments. Transporters are membrane proteins which allow molecules, such as nutrients or wastes, across membranes from one side to the other side of membrane selectively by physiological demands.

Our scientific focus

1. Molecular identification and functional studies of transporters.

Our laboratory has been focusing on molecular identifications and functional studies of transporters. Heterodimeric Amino acids Transporters (HAT) (Fig. 1) are one of our main targets. HATs form heterodimeric complexes of a heavy chain (SLC3A family) and a light chain (SLC7A family) in a unique manner, connected by an extracellular disulfide bride that is necessary to express their transport activity.

2. Amino acid transporter as a target of cancer diagnosis and therapeutics

We found that one of HAT light chains, LAT1 (L-type amino acid transporter 1; SLC7A5)is highly specifically upregulated in cancer tissues and cancer cell lines, underscoring rapid cell growth and proliferation. The cancer specific expression of LAT1 is advantageous as a molecular target of diagnosis and therapeutics of cancer. Thus, inhibition of LAT1 is expected to be a promising approach in cancer therapeutics. We are also undertaking development of novel PET probes for cancer diagnosis.

3. “Transportsome” as functional units of transporters

Recently, extending the idea of transporter complexes, we propose “Transportosome” as a functional unit of membrane transport (Fig. 2). “Transportsome” provides a functional coupling between transporters for effective solute transports, or that of transporters with enzymes for effective transport of solutes and its subsequent metabolism. Experimental evidence for the existence of “Transportsome” is accumulating and studies on their physiological or pathological significance is now on going.

4. Signaling function and sensing mechanism of amino acids

Moreover, since amino acids are not only nutrients but also biological signal factors, we propel the study of the signaling pathway via amino acids. The study mainly focuses on molecular identifications of unknown amino acids sensors. Revealing overall cellular responses/signaling events to amino acids is also in our main focus.

Fig.1 Heterodimeric Amino acids TransporterFig.2 The idea of Transportosome


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