Biology subjects

Takasu, K.

Publications and source records attributed to Takasu, K..

3 recordsLinked to original sources

bioRxiv2026

Analytical methodology for unveiling the physical effect of detergents on the function of full-length membrane proteins using a single-molecule tracking system

G protein-coupled receptors (GPCRs) are important targets for drug discovery because they are the largest and most diverse family of membrane proteins in the human body. As exemplified by {beta}2-adrenergic receptor ({beta}2AR), which is a typical class-A GPCRs, they are prone to denaturation and inactivation after solubilization. Although diverse techniques have been developed, current structural and functional analyses are still limited to proteins with relatively stable and high expression. However, some mutant variants and misfolded proteins involved in diseases have extremely low expression levels and may be difficult to analyze. To overcome these limitations, we established a novel analytical platform for evaluating the ligand-binding ability of full-length {beta}2AR as a model at the single-molecule level without purification and addressing challenges such as membrane proteins with low expression levels and structural instability. This method enables the direct use of unpurified receptors immediately after solubilization and allows us to use only a small amount of sample ([~]10 ng) for observation and to distinguish between specific and nonspecific ligand binding by fitting. Furthermore, we unveiled the physical properties of detergents on the structural stability of solubilized receptors and found that the lateral pressure within detergent micelles affects ligand-binding ability. Detergents that provided a fluid microenvironment were able to maintain ligand-binding ability for several days even after solubilization; conversely, detergents that provided a rigid microenvironment caused the protein to lose its activity earlier. Our method could be a promising tool for the structural and functional analysis of membrane proteins untargeted until now. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/740883v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@3d274corg.highwire.dtl.DTLVardef@defd0forg.highwire.dtl.DTLVardef@1b81eb4org.highwire.dtl.DTLVardef@e7c275_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Novel humanized anti-Nav1.7 antibodies with long-lasting, side-effect-free analgesic effects

Neuropathic pain remains difficult to treat effectively because of the limitations of current pain medications. The Nav1.7 sodium channel plays a crucial role in pain sensation. The development of selective inhibitors has been challenging because of the high similarity among Nav channel subtypes. To address this issue, we developed monoclonal antibodies that selectively target Nav1.7 and humanized them for clinical use for the first time. When administered systemically to neuropathic pain model rats, a potent analgesic effect was observed that lasted for at least 96 hours. Electrophysiological studies revealed that the antibody reduced mechanically-evoked and spontaneous neuronal activity in the model. Importantly, the antibodies did not impact physiological pain or motor function. Collectively, our findings suggest that these novel Nav1.7-targeting antibodies are potentially effective analgesic drugs for chronic pain, including neuropathic pain. Our novel humanized anti-Nav1.7 antibodies have the potential to be used for the development of new analgesic, and one such antibody, S-151128 is currently in clinical trial.

pharmacology and toxicology↗

bioRxiv2020

Biology and rearing of the cogongrass gall midge, Orseolia javanica Kieffer & Docters van Leeuwen-Reijnvaan (Diptera: Cecidomyiidae)

Imperata cylindrica (L.) Beauv. (Poaceae) is one of the most harmful weeds in the world because of its ability to spread and form high density, monospecific stands that exclude other vegetation. The cogongrass gall midge, Orseolia javanica Kieffer & Docters van Leeuwen-Reijnvaan (Diptera: Cecidomyiidae), is a stem galling insect that is only known to develop in cogongrass and has only been found on the island of Java in Indonesia. The midge attacks very young shoots, which stimulates abnormal growth, resulting in the formation of a purplish, elongate stem gall tappered to a point at the apical end. The aim of the current research was to describe the biology of the midge and develop a rearing method. Orseolia javanica completed its life cycle in 12-38 days with average egg, larval, and pupal periodes of 4.0 {+/-} 0.0, 13.5 {+/-} 3.8, and 8.6 {+/-} 6.6 days (mean {+/-} SD), respectively. Mated female, unmated female, and male longevities were 1.7 {+/-} 0.47, 1.2 {+/-} 0.41, and 1.0 {+/-} 0.00 days (mean {+/-} SD). Galls began to appear 29 days after larval infestation, and stem death coincided with emergence of the adult midge. The midge may have potential for biological control of cogongrass if future studies confirm a restricted host range.

ecology↗