TMEM63B channel is the mechanosensor in alveolar epithelial type II cells

Area of Science:

• Cell Biology
• Physiology
• Biophysics

Background:

• Pulmonary surfactant secretion by alveolar epithelial type II (AT2) cells is vital for lung function.
• Mechanical stretching during inspiration is the primary stimulus for this secretion.
• The precise mechanism by which AT2 cells sense mechanical stimuli has remained unclear.

Purpose of the Study:

• To identify the molecular mechanism underlying mechanical force sensing in AT2 cells.
• To investigate the role of TMEM63B as a potential mechanosensor in AT2 cells.
• To elucidate the function of TMEM63B in regulating pulmonary surfactant secretion.

Main Methods:

• Utilized Tmem63b^HA-fl/HA-fl mice for genetic deletion studies.
• Performed electrophysiological recordings to measure stretch-induced currents in AT2 cells.
• Assessed calcium (Ca²⁺) influx, lamellar body (LB) fusion, and pulmonary surfactant secretion.

Main Results:

• TMEM63B was identified as a plasma membrane protein in AT2 cells.
• Deletion of TMEM63B abolished stretch-induced currents and suppressed surfactant secretion.
• TMEM63B activation mediated Ca²⁺ influx, LB fusion, and surfactant secretion, processes impaired by TMEM63B deletion.
• ATP-induced responses were unaffected, highlighting TMEM63B's specific role in mechanotransduction.

Conclusions:

• TMEM63B functions as a critical mechanosensor in AT2 cells.
• TMEM63B is essential for sensing mechanical stretch and regulating pulmonary surfactant secretion.
• This discovery provides a key molecular target for understanding lung mechanobiology and related disorders.