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TMEM63B regulates nucleocytoplasmic transport and placental development
Mengya Cai1,2, Ruijia Lai1, Wanshan Zheng3
1Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Nature Communications
|June 8, 2026
Summary
TMEM63B, an osmo/mechano-sensitive ion channel, is crucial for placental development by regulating trophoblast cell cycle. Its loss disrupts nuclear transport, leading to placental dysfunction and perinatal lethality.
Area of Science:
- Cell Biology
- Developmental Biology
- Physiology
Background:
- Placental development relies on controlled trophoblast proliferation and differentiation, linked to cell cycle regulation.
- The integration of external cues, like mechanical forces, into cellular processes remains an area of active investigation.
Purpose of the Study:
- To identify key regulators of trophoblast cell cycle progression and placental development.
- To elucidate the role of osmo/mechano-sensitive ion channels in these processes.
Main Methods:
- Genetic manipulation to study TMEM63B function in vivo.
- Analysis of nucleocytoplasmic transport mechanisms.
- Assessment of cell cycle regulators and placental development markers.
Main Results:
- TMEM63B was identified as a critical regulator of trophoblast cell cycle and placental development.
- TMEM63B stabilizes nucleocytoplasmic transport (NCT) components, influencing the nuclear shuttling of cell cycle regulators.
- Loss of TMEM63B impairs Ran protein expression and the Ran-XPO1 complex, hindering CDKN1A/p21 nuclear export, leading to defective trophoblast proliferation and placental dysfunction.
Conclusions:
- TMEM63B is a pivotal osmo/mechano-sensitive molecule regulating nucleocytoplasmic shuttling.
- This study provides novel insights into how mechanical cues are integrated into nuclear mechanoresponses during placental development.
- TMEM63B dysfunction leads to perinatal lethality due to placental failure.
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