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Ca2+-pumping by PMCA-neuroplastin complexes operates in the kiloHertz-range
Cristina E Constantin1, Barbara Schmidt2, Yvonne Schwarz3
1Institute of Physiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nature Communications
|August 20, 2025
Summary
Plasma membrane calcium ATPases (PMCAs) are crucial for cell signaling and calcium homeostasis. This study reveals PMCA2-Neuroplastin complexes clear calcium rapidly, operating at kHz rates comparable to other transporters.
Area of Science:
- Cellular Biology
- Biochemistry
- Neuroscience
Background:
- Plasma membrane Ca2+-ATPases (PMCAs) regulate intracellular Ca2+ by extruding it from the cytosol.
- PMCAs function as complexes with Neuroplastin (NPTN) or Basigin, essential for their surface membrane localization.
- Previous studies lacked quantitative data on the pumping velocity of these complexes.
Purpose of the Study:
- To quantitatively investigate the pumping velocity of PMCA2-NPTN complexes.
- To determine the transport rates of individual PMCA2-NPTN pumps under cellular conditions.
- To compare the Ca2+ transport efficiency of PMCA2-NPTN with the Na+/Ca2+-exchanger NCX2.
Main Methods:
- Utilized Ca2+-activated K+ channels as native reporters for intracellular Ca2+ concentration.
- Employed membrane-tethered fluorescent Ca2+ indicators to monitor Ca2+ dynamics.
- Applied computational modeling based on EM-derived densities from freeze-fracture replicas.
Main Results:
- PMCA2-NPTN complexes demonstrated Ca2+ clearance in the low millisecond range.
- Computational modeling estimated individual PMCA2-NPTN pump rates exceeding 5000 cycles/s (kHz range).
- PMCA2-NPTN exhibited Ca2+ transport efficiencies comparable to the Na+/Ca2+-exchanger NCX2.
Conclusions:
- PMCA2-NPTN complexes function as high-capacity Ca2+ transporters with unanticipated kHz cycling rates.
- These findings establish PMCAs as significant contributors to rapid Ca2+ signaling termination and homeostasis.
- The study demonstrates that ATPases can operate at kHz frequencies under physiological conditions.
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