ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Kotoku Kawaguchi is first author on ‘ Ezrin knockdown reduces procaterol-stimulated ciliary beating without morphological changes in mouse airway cilia’, published in JCS. Kotoku is an assistant professor in the lab of Shinji Asano at Ritsumeikan University, Kusatsu, Japan, investigating the role of ezrin in ciliary beating and mucociliary clearance.
Kotoku Kawaguchi
How would you explain the main findings of your paper in lay terms?
To prevent infection, we have a system that carries bacteria and viruses out of our body on the surface of the airway. This system consists of many cilia, which are like brushes on the surface of cells. These cilia – motile cilia in multiciliated airway cells – are supported by various proteins in order to work well. In this study, we found that loss of ezrin, a scaffold protein, leads to suppression of drug-stimulated beating without changes to ciliary morphology in ezrin-knockdown mice. In these animals, we also found an impairment in cell surface expression of β2 adrenergic receptor (β2AR), which activates ciliary beating. Overall, our study demonstrates that ezrin regulates the beating of airway cilia by promoting the cell surface localization of β2AR.
Were there any specific challenges associated with this project? If so, how did you overcome them?
We started this study with the idea that the loss of ezrin causes abnormal ciliary morphology. However, in ezrin-knockdown mice, the morphology of airway cilia seemed to be normal, so we analyzed the surface structure in greater detail using scanning electron microscopy. Contrary to expectations, detailed analysis revealed no abnormalities in airway ciliary morphology, but we found that drug-induced activation of cilia was suppressed in ezrin-knockdown mice.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
When I found the impairment of cell surface expression of β2AR in ezrin-knockdown mice, I had a ‘eureka’ moment. In ezrin-knockdown mice, activation of ciliary beating by procaterol, a selective β2AR agonist, was suppressed. I was wondering how to understand this result, so it was a most exciting moment for me to see a clue to the solution.
In ezrin-knockdown mice, procaterol-stimulated beating is reduced due to disturbed apical localization of β2AR. Ezrin and β2AR are localized with F-actin in the apical region in wild-type (WT) mice. However, the apical localization of β2AR is disturbed in ezrin-knockdown (Vil2kd/kd) mice. Scale bars: 5 μm. AcTub, acetylated tubulin; CBA, ciliary bend angle; CBF, ciliary beat frequency.
In ezrin-knockdown mice, procaterol-stimulated beating is reduced due to disturbed apical localization of β2AR. Ezrin and β2AR are localized with F-actin in the apical region in wild-type (WT) mice. However, the apical localization of β2AR is disturbed in ezrin-knockdown (Vil2kd/kd) mice. Scale bars: 5 μm. AcTub, acetylated tubulin; CBA, ciliary bend angle; CBF, ciliary beat frequency.
Why did you choose Journal of Cell Science for your paper?
I am grateful to regularly read Journal of Cell Science for the beautiful results and cutting-edge research on cell biology. In addition, we chose JCS because JCS always publishes research reports of high scientific value.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I've been interested in explaining phenomena in physics and other sciences with general theories since I was a high school student. When I could not get a good result by immunostaining when I was a PhD student, I examined the experimental conditions one by one and finally got a satisfactory result. This was the most interesting moment. I would like to contribute to basic research by clarifying biological phenomena, leading to ideas for the development of new therapeutic agents and treatments.
Who are your role models in science? Why?
I respect Professor Shinji Asano, my PI, as a scientist. I especially respect his passion for his work.
Tell us something interesting about yourself that wouldn't be on your CV
I like shogi (Japanese chess) – it is an exciting game. This game trains us to think logically. I also like Java sparrows. They give me everyday healing.
Kotoku Kawaguchi's contact details: Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University,1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan.
E-mail: [email protected]
