Related Experiment Video

Updated: Jan 31, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

9.9K

PKCϵ-mediated phosphorylation of TRPC3 channel at S712 is essential for its inactivation during inflammatory

Javier Casas1,2, Clara Meana1,3,4, Gonzalo San-José1

  • 1Lipid Metabolism and Inflammation Group, IBGM, CSIC-UVA, Valladolid, Spain.

Frontiers in Immunology
|January 30, 2026
PubMed

Insights

Protein kinase C epsilon (PKCϵ) inactivates the TRPC3 channel via S712 phosphorylation, resolving inflammatory calcium signals in macrophages. This mechanism is crucial for controlling inflammatory responses during LPS activation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The transient receptor potential canonical 3 (TRPC3) channel is vital for macrophage inflammatory signaling.
  • Intracellular calcium dynamics are key regulators of inflammatory processes.

Purpose of the Study:

  • To identify the regulatory mechanism of TRPC3 channel activity in macrophages.
  • To elucidate the role of protein kinase C epsilon (PKCϵ) in TRPC3 channel regulation during inflammation.

Main Methods:

  • Utilized HEK-TLR4 cells and THP-1 human macrophages.
  • Employed S712A-TRPC3 mutant to assess phosphorylation effects.
  • Conducted live-cell imaging and FRET assays.
  • Performed pharmacological inhibition and gene silencing of PKCϵ.

Main Results:

  • PKCϵ phosphorylates TRPC3 at S712, leading to channel inactivation.
  • S712A-TRPC3 mutant shows persistent calcium influx and increased TNFα and COX2 expression.
  • PKCϵ translocation to endomembranes and interaction with TRPC3 upon LPS stimulation confirmed.
  • PKCϵ inhibition or silencing mimicked the S712A mutation effects.

Conclusions:

  • PKCϵ-mediated phosphorylation of TRPC3 at S712 is a critical mechanism for TRPC3 channel inactivation.
  • This phosphorylation event is essential for resolving inflammatory calcium signaling in macrophages.
  • The findings highlight a key regulatory pathway in macrophage-mediated inflammation.
Keywords:
TRPC3 channelscalciuminflammationmacrophageprotein kinase C (PKC)

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