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DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells

Tiernan J Mulrooney1, Phillip E Posch, Carolyn Katovich Hurley

  • 1Georgetown University Medical Center, Research Building, Room E404, Georgetown University Medical Center, 3970 Reservoir Rd., N.W., Washington, DC 20057, USA.

Journal of Leukocyte Biology
|May 30, 2013
PubMed

Insights

The adapter DAP12 influences the surface expression and stability of KIR2DS receptors on natural killer (NK) cells. Reduced DAP12 levels may impair NK cell function by affecting KIR2DS interactions.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Killer cell immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cell activity.
  • The adapter DAP12 is known to be involved in KIR-mediated signaling.
  • The role of DAP12 in KIR2DS surface expression and stability was not fully understood.

Purpose of the Study:

  • To investigate the effect of the interaction between KIR2DS and DAP12 on KIR2DS surface expression and stability.
  • To elucidate the mechanism by which DAP12 influences KIR2DS trafficking and cell surface presentation.

Main Methods:

  • Flow cytometry to analyze KIR2DS surface expression.
  • siRNA to knockdown DAP12 expression.
  • Cycloheximide (CHX) and Brefeldin A (BFA) treatment to study protein synthesis and trafficking.
  • Immunoprecipitation to detect protein interactions.
  • Internalization assays and confocal microscopy to assess surface stability and localization.

Main Results:

  • DAP12 cotransfection enhanced KIR2DS surface expression, while DAP12 knockdown decreased it.
  • DAP12 facilitates the trafficking of newly synthesized KIR2DS to the cell surface.
  • DAP12 interacts with an immature KIR2DS isoform in the endoplasmic reticulum (ER).
  • DAP12 significantly impacts KIR2DS surface stability, though internalized receptors are lysosomally targeted independently of DAP12.

Conclusions:

  • DAP12 plays a crucial role in the surface expression and stability of KIR2DS.
  • Reduced DAP12 expression in vivo could impair NK cell recognition and signaling through KIR2DS.
  • These findings highlight a novel regulatory mechanism for NK cell receptor presentation and function.
Keywords:
innate immunityreceptor internalizationreceptor maturation

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