Information flow in a biological context (bioinformation) consists of genetic information that flows from DNA to proteins through RNA, intercellular information that flows from one cell to another (in cell adhesion, recognition, and intracellular signal transduction), and environmental information that flows from the environment to the cell. A noted property of bioinformation flow is that the highest efficiency in transferring a large amount of information is through a small apparatus. Thanks to information from the human genome, which has been determined in recent years, we now can easily understand the structural features of various proteins that are involved in transferring bioinformation. However, it is still mysterious how individual genetic products (proteins) are incorporated into molecular complexes or apparatuses that are responsible for the flow of bioinformation. The roles played by glycan chains present in the molecular complex in the transfer of bioinformation are also not understood. In particular, glycan chains are interesting in that they are always part of the molecular complex on cells, although the reasons for this are not clear, and that they are situated at the outermost part of the cell surface. Furthermore, glycan chains show high structural diversity, arising from complicated branched structures that cannot be predicted from genetic information, and also show a heterogeneity of structure that occurs even in a single glycan chain on a single protein. “Diversity” and “heterogeneity” would be key concepts, if the glycans truly play a role in the transfer of bioinformation. Thus, our research goal is to understand how glycan chains function as an important part of the hardware of bioinformation transfer on the cell surface.
First, we focus on membrane microdomains, which are 50 to 500 nanometers in diameter and are rich in glycan chains. It has recently been shown that membrane microdomains are recognized as a site of signal exchange between the outside and inside of the cell, or a hot spot for signal transduction, because they contain various adhesion and receptor molecules together with signal transducers. In addition, the membrane microdomains contain a unique feature in that they are enriched in glycan chains. Recently, we have actually demonstrated that membrane microdomains are involved in glycan chain-mediated interactions as well as signal transduction in the sperm-egg interaction. Since glycan chains can provide an astronomical amount of information due to their structural diversity, membrane microdomains are recognized as a molecular apparatus for processing massive and various kinds of information. Thus, these features have prompted us to consider that membrane microdomains are intelligent and highly efficient nano-devices for glycan-mediated recognition and binding as well as for signal transduction. In our research group, we aim to (1) carry out biochemical and chemical characterization of components and determine their interactions in the membrane microdomains, and (2) understand the roles of membrane microdomains in cell adhesion and ligand-receptor binding, focusing on the combined effects of each component that is involved in these biological phenomena.
Second, we focus on sialic acids in that their structures show extraordinarily high diversity and heterogeneity.
Why do we study on lower animals as well as mammals?
The biological significance of glycan chains in cell adhesion is not well understood, although these molecules are ubiquitous on the cell surfaces of bioorganisms on earth. This absence of information is largely due to the difficulty in determining the structures precisely, because glycan chains intrinsically contain diversity and heterogeneity in their structures. Unlike nucleic acids and proteins, the structures of glycan chains are not easily deduced from the linear information of nucleic acids, but rather by laborious chemical methods. In our project, we determine the structures of glycan chains in membrane microdomains by collecting a relatively large amount of material, which allows us to analyze the chemical structures in detail. For this purpose, we chose invertebrate (sea urchin) fertilization and fish (medaka fish) early development as model systems. Our research will reveal what types of glycan chains play important roles in various cell adhesion events, and will establish a molecular basis for glycan chain-mediated interactions in cell adhesion events.
We also focus on microdomains as a molecular complex consisting of proteins, lipids, and glycan chains in these cell adhesion events. Such a complex structure may be important to fulfill highly efficient, bioinformational roles, as in the case of the cell. Very few studies have been carried out to analyze the role of such molecular complexes, while many studies have been done on the interactions between two purified proteins. In this regard, our project is novel in that we will attempt to understand the role of each component in microdomains by ultimately reconstituting a molecular complex of functional equivalence to the isolated membrane microdomains. Our project is regarded as a challenge to understand the merits of complex formation of heterogeneous materials like proteins, lipids, and glycan chains. In particular, we are expecting that glycan chains may add informational properties not present in simple, straightforward protein-protein interactions, because glycan chain-mediated interactions show a rapid dissociation-association equilibrium with a weak binding affinity, in contrast to protein-mediated interactions, which are characterized by a slow dissociation-association equilibrium with a strong binding affinity.
What are merits of our studies?
Membrane microdomains can be considered to be highly efficient, minimum size apparatuses that contain informational properties essential to a biological system. If we succeed in understanding and reconstituting the membrane system, our results may be of great influence on material sciences, such as polymer science and liposome engineering. We may switch a protein-based interaction (hard interaction) to a glycan chain-based interaction (soft interaction) on a single device, if we put both protein and glycan chains on the same apparatus. Since glycan chains bear diverse and heterogeneous structures in a single chain, we may be able to incorporate various types of information (structures) on a single device. This device is in reality in the cell, but as yet, it has not been recognized as an ideal material. Considering that bioorganisms are the most efficient instruments on earth, this type of glycan chain-based material may have some novel features that we are currently unable to predict or understand.