New proteins involved in regulating the cell membrane
Graduate student at Graduate School of Biostudies, Kyoto University (Suzuki Lab)
Niu Han
Niu Han
Niu Han is a graduate student who studies the dynamics of cell membrane phospholipids at Kyoto University. In her recent study, she discovered that two functional proteins form complexes that perform a new function, providing theoretical support for phospholipid scrambling associated with anemia and epilepsy.
Please share with us the significance of your manuscript in terms of its research achievements, impact, or uniqueness.
Cell membrane proteins serve critical roles as ion channels, transporters, receptors, and more, each contributing uniquely to cellular processes and maintaining homeostasis. This study reveals a new mechanism in which two membrane proteins exhibit distinct activity from their original functions, by forming a complex.
Through unbiased CRISPR-sgRNA library screening and biochemical screening, the mechanosensitive cation channel Tmem63b was identified as a phospholipid scrambling-inducing factor and shown to exhibit scrambling activity by forming a complex with the thiamine transporter Slc19a2.
Mutations in the Tmem63b gene have been reported to be linked to neurodegenerative and hematological disorders. In this study, it was found that Tmem63b mutants exhibit continuous scrambling activity that disrupts the asymmetric distribution of phosphatidylserine (PS) in cell membranes. When PS is exposed on the outer leaflet of the cell membrane, it acts as an ”eat me” signal, attracting macrophages to perform phagocytosis. This mechanism in red blood cells may explain why patients with mutant Tmem63b experience hematological disorders, such as anemia.
This study underscores the significant potential for protein-protein interactions and offers insights that could guide the theoretical exploration of anemia therapies.
Please tell us what was the most gratifying or inspiring moment for you during this research project.
The moment when I detected the dimer band in my BN-PAGE result is still vivid in my memory. I remember the first time when I saw the result—it was so clear and the difference was so obvious. That trial was just a casual attempt, and I did not have any particular expectations, but it completely surprised me and motivated me to complete the entire research. Honestly, this was the most impressive moment I experienced during this study.
Please tell us about the biggest challenge or problem you experienced while conducting your research. How did you overcome it?
When I was strung out across multiple tasks, I needed to handle all the tasks and I felt I couldn’t do any of them without mistakes. At that time I felt pressured and so unsure of myself. But then I realized I needed to be proactive rather than passive, and I started to welcome everything and worked to understand my limitations. I think choosing an imperfect variety over a flawless focus is wiser for me, as it deepens my self-understanding and fosters a positive mentality towards challenges.
Would you consider this work to be a turning point in your overall research direction? If so, how has your research direction changed as a result of this work?
Yes, this work could be a turning point that guides my future research direction. It has inspired me both in life and research. It gave me greater confidence in my ability and a sense of recognition of my efforts. Additionally, it opened up a new perspective on the different ways in which proteins attain activity, renewing my understanding of how proteins work. I am looking forward to investigating whether this mechanism is a universal feature in dynamic cellular processes. Since it is potentially linked to human diseases, I am hopeful this work could contribute to disease therapy in the future.
Please describe the current situation of your career. What is your current position? How has the knowledge and experience gained at iCeMS influencing your career?
I am currently studying at Kyoto University as a researcher. iCeMS offers a good environment for academic communication, with frequent academic reports, events, and activities. It provides a good platform to listen to others’ work and also share your findings. While enjoying these experiences, I have also grown personally. I have learned how to enhance my posters and how to present myself, thanks to the practice opportunities provided by Suzuki Lab and iCeMS. My time at iCeMS has been truly unforgettable.
Paper information
"Phospholipid scrambling induced by an ion channel/metabolite transporter complex."
Authors: Niu Han, Masahiro Maruoka, Yuki Noguchi, Hidetaka Kosako, and Jun Suzuki.
Published: August 2024