The intrinsically disordered region from PP2C phosphatases functions as a conserved CO₂ sensor.

Area of Science:

• Cellular Biology
• Biochemistry
• Environmental Science

Background:

• Carbon dioxide (CO2) is vital for the carbon cycle and cellular signaling.
• Organisms must adapt to changing CO2 concentrations for survival.
• Current understanding suggests carbonic anhydrases transduce CO2 changes, but direct CO2 sensing mechanisms remain elusive.

Purpose of the Study:

• To identify the molecular mechanisms by which organisms sense carbon dioxide (CO2).
• To investigate the role of PP2C phosphatases in CO2 sensing.
• To elucidate how CO2 sensing regulates cellular programs.

Main Methods:

• Investigated a unique group of PP2C phosphatases from fungi and plants.
• Utilized in vitro and in-cell experiments to observe phase separation.
• Analyzed the role of intrinsically disordered regions (IDRs) in CO2 sensing and PP2C activation.

Main Results:

• Identified specific PP2C phosphatases that directly sense CO2, but not bicarbonate (HCO3-).
• Demonstrated that these PP2Cs possess intrinsically disordered regions (IDRs) crucial for their function.
• Observed that PP2Cs form reversible, liquid-like droplets via phase separation in response to elevated CO2.
• Showcased IDR-mediated phase separation as a CO2-responsive activation mechanism.

Conclusions:

• PP2C phosphatases act as direct CO2 sensors in diverse cellular programs.
• Intrinsically disordered regions (IDRs) within PP2Cs are key to their CO2 responsiveness.
• IDR-mediated phase separation provides a novel mechanism for direct CO2 sensing in biological systems.