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CD43 processing and nuclear translocation of CD43 cytoplasmic tail are required for cell homeostasis

Wooseok Seo1, Hermann J Ziltener

  • 1The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.

Blood
|August 22, 2009
PubMed

Insights

The sialomucin CD43 ectodomain shedding is crucial for cell survival. Its cytoplasmic tail

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Sialomucin CD43 is highly expressed on hematopoietic cells.
  • CD43 shedding varies across different cell types, notably absent in macrophages.

Purpose of the Study:

  • Investigate the functional significance of CD43 ectodomain shedding.
  • Determine the role of CD43 cytoplasmic tail (CD43ct) in cell homeostasis and apoptosis.

Main Methods:

  • Constructed CD43/34 chimeras to study domain swapping effects.
  • Analyzed cell viability and toxicity of chimera expression.
  • Investigated CD43ct nuclear translocation and its interaction with SUMO-1 and PML bodies.
  • Assessed apoptosis sensitivity in CD43-deficient cells.

Main Results:

  • CD43 ectodomain shedding is specific to granulocytes, mast cells, and T cells.
  • Forced expression of CD43/34 chimeras negatively impacted cell viability.
  • CD43ct translocation to the nucleus and gamma-secretase-mediated release were proapoptotic.
  • CD43 deficiency led to reduced PML bodies and increased apoptosis sensitivity.

Conclusions:

  • CD43 processing and nuclear localization of its cytoplasmic tail are essential for cell homeostasis.
  • CD43 plays a critical role in regulating apoptosis in hematopoietic cells.

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