Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.
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2022-06-07
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TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.
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Zhang, Yang, Pengfei Liang, Liheng Yang, Ke Zoe Shan, Liping Feng, Yong Chen, Wolfgang Liedtke, Carolyn B Coyne, et al. (2022). Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion. eLife, 11. p. e78840. 10.7554/elife.78840 Retrieved from https://hdl.handle.net/10161/25516.
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Scholars@Duke
Liping Feng
Liping Feng, MD's research has focused on understanding the mechanisms of pregnancy complications associated with placental development. These works are translated then to the clinical care of women through studies dedicated to identify risk factors and novel biomarkers for early prediction and prevention of adverse birth outcomes.
Dr. Feng devotes her entire career to improving pregnancy outcomes through innovative research. Dr. Feng conducts both basic science/laboratory research, as well as participates in clinical studies. Her laboratory has focused on understanding the mechanisms of placenta-originated pregnancy complications such as preeclampsia and still birth, which are important causes of perinatal and neonates’ mortality and morbidity. Currently, she has three lines of investigation focused on the roles of inflammation/infection, cell aging, and environmental exposure in placental development and subsequent pregnancy complications.
In addition, Dr. Feng has established an international collaboration in Global Women’s Health. She has affiliated with the Duke Global Health Institute (DGHI) and participates in a DGHI research. She has an interest in DGHI education, and service or policy initiatives, including mentoring and teaching graduate and professional students on fieldwork and research.
Yong Chen
Dr. Yong Chen is an Associate Professor of Neurology at the Duke University School of Medicine. He is also affiliated with Duke Anesthesiology-Center for Translational Pain Medicine (CTPM) and Duke-Pathology.
The Chen lab mainly studies sensory neurobiology of pain and itch, with a focus on TRP ion channels and neural circuits. The main objective of our lab is to identify molecular and cellular mechanisms underlying chronic pain and chronic-disease associated itch, using a combination of animal behavioral, genetic, molecular and cellular, advanced imaging, viral, and optogenetic approaches. There are three major research areas in the lab: craniofacial pain, arthritis pain and joint function, and systemic-disease associated itch.
Wolfgang Bernhard Liedtke
Research Interests in the Liedtke-Lab:
- Pain/ nociception
- Sensory transduction and -transmission
- TRP ion channels
- Water and salt equilibrium regulated by the central nervous system
Visit the lab's website, download papers and read Dr. Liedtke's CV here.
Carolyn Coyne
We study the pathways by which microorganisms cross cellular barriers and the mechanisms by which these barriers restrict microbial infections. Our studies primarily focus on the epithelium that lines the gastrointestinal tract and on placental trophoblasts, the cells that comprise a key cellular barrier of the human placenta. Our work is highly multidisciplinary and encompasses aspects of cell biology, immunology, and microbiology. Our long-term goals are to identify pathogen- and host-specific therapeutic targets to prevent or treat microbial infections and ultimately to alleviate the morbidity and mortality caused by these infections.
Huanghe Yang
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