Molecular Signal Transduction

Outline of Research and Education

Signal transduction is indispensable for organ development and homeostasis. Hormones and neurotransmitters induce a variety of cell responses mediated through membrane receptors and intracellular signaling pathways. Impairment of the signal transduction often causes disease. And with this, many drugs targeting these signal components are widely used today. Our laboratory is interested in cellular signaling systems with special emphasis on heterotrimeric G proteins. In our laboratory, faculty and graduate students are dedicated to cutting-edge scientific research and work towards a better understanding of how the human body functions and the alleviation of human disease.

Major Research Topics

Cellular functions and regulatory mechanisms of G protein signaling

Heterotrimeric GTP-binding regulatory protein (G protein) consists of α, β and γ subunits, and is activated by seven-span transmembrane receptors, G protein-coupled receptors (GPCRs). G proteins transduce extracellular signals to downstream effecter molecules and are involved in many aspects of cellular physiology. Recently, a small molecule and several gene products that regulate the G protein signaling have been discovered. We try to clarify the new regulatory mechanisms and functions of G protein signaling using these molecules. Cross talk and interaction between different signaling pathways are also studied.

Molecular mechanisms of self-renewal, differentiation, and migration of neural stem cells

Neural stem cell that can differentiate into neuron and glia exist in not only embryo but also adult brain. However, the mechanism for self- renewal, asymmetric cell division and migration during brain development remains obscure. Using slice culture, neurosphere culture and in ovo microinjection with virus-vectors, we attempt to understand the molecular mechanisms. More recently, we found the dual regulation of neuronal progenitor cell migration by distinct G protein signals mediated through dynamic cytoskeleton rearrangements.

Monoclonal antibodies against orphan adhesion GPCRs involved in tumorigenesis and neural function

More than 200 members of GPCRs are orphan receptors that miss endogenous ligands. We prepared the monoclonal antibodies against adhesion GPCR, GPR56, and obtained the functional antibody that acts as an agonist. This antibody inhibits cancer cell migration in vitro system. Using newly identified antibodies, we analyze the function and activation mechanism of orphan adhesion GPCRs, and approach the drug development.

Regulation of primary cilia formation and function in mammalian cells

Primary cilia function as cellular antennae to sense extracellular environment and transduce signals to the cell. Defects in the organelle associate with many disorders including genetic diseases called ciliopathies and cancer. We are attempting to elucidate molecular mechanisms that underlie assembly and function of primary cilia in mammalian cells and interested in application to human diseases..

Molecular mechanisms of epithelial morphogenesis and cancer

Epithelial tissue remodels its shape to tubular or acinar structure during organ development. In the epithelial morphogenesis, various processes such as cell proliferation, migration, adhesion, and polarization are coordinately regulated, and the disruption of epithelial architecture is one of the hallmarks of cancer. We study molecular mechanisms regulating epithelial morphogenesis by using 3-dimensional cell culture.


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Fig.1 Signal transduction mediated by G protein- coupled receptor
Fig.1 Signal transduction mediated by G protein- coupled receptor
Fig.2 G protein/PKA signal-regulated dynamics of a cytoskeleton in neuronal progenitor cells
Fig.2 G protein/PKA signal-regulated dynamics of a cytoskeleton in neuronal progenitor cells
Fig.3 Monoclonal antibody against orphan GPCR as a tool for signal analysis
Fig.3 Monoclonal antibody against orphan GPCR as a tool for signal analysis
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