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Updated: Aug 7, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Phosphatidylinositol-3 phosphatase myotubularin-related protein 6 negatively regulates CD4 T cells

Shekhar Srivastava1, Kyung Ko, Papiya Choudhury

  • 1Department of Pharmacology, The Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.

Molecular and Cellular Biology
|July 19, 2006
PubMed

Insights

Myotubularin-related protein 6 (MTMR6) inhibits the KCa3.1 channel, a key player in T-cell activation. This finding reveals MTMR6

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • T-cell activation involves a rapid rise in intracellular calcium (Ca2+) levels, mediated by the T-cell receptor (TCR).
  • Potassium (K+) channels are crucial for maintaining the membrane potential necessary for driving Ca2+ influx into T lymphocytes.

Purpose of the Study:

  • To investigate the role of the Ca2+-activated K+ channel, KCa3.1, in T-cell activation.
  • To elucidate the regulatory mechanism of KCa3.1 by phosphatidylinositol-3 phosphate (PI(3)P) and its associated phosphatases, specifically myotubularin-related protein 6 (MTMR6).

Main Methods:

  • Investigated the interaction between KCa3.1, PI(3)P, and MTMR6 in reactivated naive and central memory T cells.
  • Assessed the impact of MTMR6-mediated inhibition of KCa3.1 on Ca2+ influx and proliferation in human CD4 T cells.

Main Results:

  • The Ca2+-activated K+ channel, KCa3.1, requires PI(3)P for its activation.
  • Myotubularin-related protein 6 (MTMR6) inhibits KCa3.1 channel activity.
  • MTMR6 acts as a negative regulator of Ca2+ influx and proliferation in reactivated human CD4 T cells by inhibiting KCa3.1.

Conclusions:

  • MTMR6 plays a significant role in regulating Ca2+ influx in activated CD4 T cells.
  • MTMR6 is critical in establishing a threshold for T-cell activation, highlighting a novel regulatory pathway involving PI(3)P and MTMR6.

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