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Co-expression of MG29 and ryanodine receptor leads to apoptotic cell death: effect mediated by intracellular Ca2+

Zui Pan1, Yutaka Hirata, Ramakrishnan Y Nagaraj

  • 1Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

The Journal of Biological Chemistry
|March 25, 2004
PubMed

Insights

Mitsugumin 29 (MG29) interacts with the ryanodine receptor (RyR), enhancing its activity. This interaction disrupts calcium homeostasis, leading to apoptosis, particularly in muscle cells.

Area of Science:

  • Cellular Biology
  • Molecular Physiology
  • Muscle Physiology

Background:

  • Intracellular calcium (Ca2+) homeostasis is crucial for cell proliferation and apoptosis.
  • Mitsugumin 29 (MG29), a protein in skeletal muscle triads, regulates Ca2+ signaling and store-operated Ca2+ entry.
  • The ryanodine receptor (RyR) is a key Ca2+ release channel in muscle cells.

Purpose of the Study:

  • To investigate the functional interaction between MG29 and the RyR/Ca2+ release channel.
  • To determine the effects of MG29 and RyR co-expression on cellular viability and Ca2+ homeostasis.
  • To elucidate the role of MG29-RyR interaction in muscle Ca2+ signaling and apoptosis.

Main Methods:

  • Purification and functional reconstitution of MG29 protein into lipid bilayer membranes.
  • Co-expression of MG29 and RyR in Chinese hamster ovary (CHO) cells.
  • Transient expression studies to analyze protein localization and cellular effects.

Main Results:

  • Purified MG29 enhances the activity of the incorporated RyR/Ca2+ release channel.
  • Co-expression of MG29 and RyR in CHO cells induces apoptotic cell death due to intracellular Ca2+ store depletion.
  • RyR expression causes MG29 retention in intracellular organelles, preventing plasma membrane localization.

Conclusions:

  • A functional interaction exists between MG29 and RyR, impacting Ca2+ signaling.
  • Perturbation of Ca2+ homeostasis by MG29-RyR interaction is a key signal for apoptosis initiation.
  • This interaction has significant implications for Ca2+ signaling in muscle cells.

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