Elucidation of the Physiological Functions of Membrane Proteins as Novel Drug Target Candidate Molecules.

Abstract

For pharmaceutical research focused on identifying novel drug target candidate molecules, it is essential to explore unknown biological phenomena, elucidate underlying molecular mechanisms and regulate biological processes based on these findings. Proteins expressed on the plasma membrane and endoplasmic reticulum (ER) membrane play important roles in linking extracellular environmental information to intracellular processes. Stimulating membranous proteins induces various kinds of changes in cells, such as alterations in gene expression levels and enzymatic activities. However, the physiological functions and endogenous ligands of many G-protein-coupled receptors (GPCRs) have not been determined, although GPCRs already constitute a large class of drug-target membrane proteins. Furthermore, the precise physiological roles played by many ER membrane proteins have not been elucidated to date. In this review article, I summarize the results of our recent studies, including the observations that the lipid sensor FFAR4/GPR120 controlled systemic energy homeostasis and that the ER membrane monovalent cation channel trimeric intracellular cation (TRIC)-B and the plasma membrane divalent cation channel transient receptor potential melastatin 7 (TRPM7) regulated bone formation. I further describe the therapeutic significance of these membranous protein-related biological processes.