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Membrane potential modulates ERK activity and cell proliferation in human cells.

Mari Sasaki1, Masanobu Nakahara1, Takuya Hashiguchi1

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Membrane depolarization, or a shift in electrical charge, drives cell division (mitosis) in human cells by activating extracellular signal-regulated kinase (ERK). This discovery reveals new roles for membrane potential in regulating cell proliferation.

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ERKcell biologyhumanhuman cellsimagingmembrane potentialproliferation

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Area of Science:

  • Cell Biology
  • Biophysics
  • Physiology

Background:

  • Plasma membrane potential is known to influence cell proliferation in vertebrate cells.
  • The precise mechanisms linking membrane potential to proliferation require further elucidation.

Purpose of the Study:

  • To experimentally demonstrate the link between membrane depolarization and cell proliferation in human cells.
  • To investigate the role of extracellular signal-regulated kinase (ERK) in this process.
  • To explore the underlying biophysical mechanisms.

Main Methods:

  • Experimental manipulation of plasma membrane potential.
  • Measurement of cell proliferation (mitosis).
  • Assay of extracellular signal-regulated kinase (ERK) activity.
  • Analysis of phosphatidylserine dynamics and calcium influx.

Main Results:

  • Membrane depolarization was shown to promote mitosis in human cells.
  • ERK activation was found to be voltage-dependent and crucial for depolarization-induced proliferation.
  • ERK activity was independent of growth factor stimulation and linked to phosphatidylserine dynamics, not calcium influx.
  • Small shifts in resting membrane potential were sufficient to influence proliferative activity.

Conclusions:

  • Plasma membrane potential directly regulates cell proliferation in human cells via voltage-dependent ERK activation.
  • This mechanism involves altered phosphatidylserine dynamics, independent of calcium.
  • The findings expand the known physiological roles of membrane potentials beyond neural systems, highlighting their importance in fundamental cellular processes.