Bio-system Pharmacology
- The function of amino acid transporters on amino acid signaling
- Construction of the "transportsome" to describe the relationship between transporters and cellular functions
- Proteome and metabolome analysis for the role of transporters in cell and tissue functions
- Imaging and therapeutics targeting amino acid transporter function in cancers
To reveal physiological and pathological roles of amino acid transporters and amino acid signaling and to develop new diagnostic and therapeutic drugs targeting them
Transporters are membrane proteins that regulate the permeation of intracellular and extracellular substances through the cell membranes. Amino acid transporters supply amino acids to the cells and also mediate the absorption of amino acids into the body at the small intestine and kidney epithelia. Although several major amino acid transporters have been identified, their roles in physiological and pathological function are not well explored. We are therefore investigating the molecular functions and dynamics of amino acid transporters in biological systems.
Conventional transporter research has mostly focused on the function of individual transporters. However, multiple transporters coordinate for physiological functions, as seen in the transepithelial transport. In addition, transporters crosstalk with intracellular signaling systems. Therefore, we have proposed the concept of the "transportsome", which describes the complex network of transporters and related molecules
Fig. 1 The concept of Transportsome
In addition, we have reported that LAT1 (L-type amino acid transporter 1) is up-regulated in various cancer cells and cancer tissues. LAT1 contributes to the proliferation capacity and malignancy of cancer cells and its inhibition can suppress these phenotypes. We have since used LAT1 as a diagnostic imaging marker of cancer and a target for drug development. More recently, it has become clear that leucine is a signaling molecule in the mTORC1 pathway, which controls cellular metabolism. In several diseases such as cancer and diabetes, it is proposed that the aberrated mTORC1 signaling is involved in the pathogenesis of diseases. We are investigating the signals downstream of LAT1 to reveal their roles in cellular functions. We are particularly interested in the molecular mechanisms to recognize leucine to understand overall scheme of the amino acid signaling mediated by amino acid transporters that regulates cellular metabolism and functions
Fig. 2 Research projects related to LAT1, a cancer-type amino acid transporter
