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TRPM5 activation depends on a synergistic effect of calcium and PKC phosphorylation

Alaa Nmarneh1, Avi Priel2

  • 1The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, Jerusalem, 9112102, Israel.

Communications Biology
|March 28, 2024
PubMed

Insights

Protein kinase C (PKC) phosphorylation and increased intracellular calcium are essential for activating the TRPM5 channel. This discovery offers new therapeutic targets for diseases involving TRPM5 modulation.

Area of Science:

  • Ion channel physiology
  • Molecular pharmacology

Background:

  • Transient receptor potential melastatin 5 (TRPM5) is a calcium-activated ion channel critical for insulin secretion and taste.
  • TRPM5 activation is linked to Gq/G-protein coupled receptors (GPCRs) and intracellular calcium elevation.
  • The precise molecular mechanisms governing TRPM5 activation remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular determinants required for TRPM5 channel activation.
  • To investigate the roles of intracellular calcium and protein kinase C (PKC) phosphorylation in TRPM5 function.

Main Methods:

  • Electrophysiological recordings in cells expressing TRPM5.
  • Pharmacological manipulation of intracellular calcium levels.
  • Assessment of PKC activity and its effect on TRPM5 currents.

Main Results:

  • TRPM5 channel activation necessitates both PKC phosphorylation and elevated intracellular Ca2+ levels.
  • PKC phosphorylation is critical for TRPM5 currents at physiological membrane potentials.
  • Elevated calcium alone activates TRPM5 only at positive voltages.

Conclusions:

  • Coordinated intracellular calcium release and PKC phosphorylation are essential for TRPM5 activation.
  • Modulating PKC activity presents a potential therapeutic strategy for TRPM5-related diseases.

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