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Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
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Tmem178 negatively regulates store-operated calcium entry in myeloid cells via association with STIM1

Zhengfeng Yang1, Hui Yan1, Wentao Dai2

  • 1Department of Orthopaedics, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Journal of Autoimmunity
|April 26, 2019
PubMed

Insights

Transmembrane protein 178 (Tmem178) acts as a negative regulator of store-operated calcium entry (SOCE) by inhibiting STIM1 puncta formation in myeloid cells, impacting inflammatory responses.

Area of Science:

  • Cellular Biology
  • Immunology
  • Calcium Signaling

Background:

  • Store-operated calcium entry (SOCE) regulates intracellular calcium levels, crucial for cellular functions.
  • STIM1 and ORAI1 are key proteins in SOCE, requiring STIM1 oligomerization and puncta formation for activation.
  • Negative regulation of SOCE is vital to prevent calcium overload, but remains poorly understood.

Purpose of the Study:

  • To identify negative regulators of STIM1 puncta formation in myeloid cells.
  • To elucidate the role of Tmem178 in the modulation of SOCE.
  • To investigate the impact of Tmem178 on inflammatory processes.

Main Methods:

  • Site-directed mutagenesis to study Tmem178:STIM1 interactions.
  • Co-immunoprecipitation assays to confirm protein association.
  • FRET imaging to visualize Tmem178 and STIM1 dynamics.
  • Assessment of SOCE activation, cytokine production, and osteoclastogenesis.

Main Results:

  • Tmem178 negatively regulates STIM1 puncta formation via interaction with STIM1's transmembrane domain.
  • Increased Tmem178:STIM1 association reduces SOCE, inflammatory cytokine production, and osteoclastogenesis.
  • Decreased Tmem178 expression in arthritic patients correlates with enhanced SOCE and cytoplasmic calcium.

Conclusions:

  • Tmem178 is a critical negative modulator of STIM1 puncta formation, controlling the rate-limiting step of SOCE.
  • Tmem178 plays a significant role in regulating calcium homeostasis during inflammatory conditions.
  • Targeting Tmem178 may offer therapeutic potential for inflammatory diseases.
Keywords:
Macrophage activationOsteoclastogenesisSOCESTIM1Tmem178

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