The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein

J Dedio1, W Jahnen-Dechent, M Bachmann

  • 1Institute for Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University at Mainz, Germany.

Insights

The C1q receptor (gC1qR) is found in mitochondria, not on cell surfaces. This mitochondrial localization suggests its role as a complement receptor needs re-evaluation.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • The 33 kDa protein (p33), also known as the globular C1q receptor (gC1qR), is believed to be the primary C1q receptor on immune cells.
  • The cellular localization and trafficking of p33/gC1qR have not been previously determined.

Purpose of the Study:

  • To investigate the subcellular localization and cellular routing of the p33/gC1qR.
  • To determine if p33/gC1qR is expressed on the cell surface or within intracellular compartments.

Main Methods:

  • Confocal laser-scanning microscopy was used to examine p33/gC1qR localization in cells.
  • Immunofluorescence microscopy and transfection studies with green fluorescent protein (GFP) fusion proteins were employed.
  • Immunocytochemistry was performed on fetal mouse tissues.

Main Results:

  • p33/gC1qR was found in intracellular compartments, colocalizing with the mitochondrial marker pyruvate dehydrogenase.
  • No surface expression of p33/gC1qR was detected on endothelial cells.
  • The N-terminal 33 amino acids of p33/gC1qR were sufficient to direct reporter proteins to mitochondria.
  • The mature p33/gC1qR protein (209 residues) was localized to the mitochondrial matrix and/or inner membrane.
  • p33/gC1qR showed ubiquitous expression in fetal mouse tissues, particularly in mitochondria-rich tissues.

Conclusions:

  • The candidate complement receptor p33/gC1qR is localized within mitochondria, not on the cell surface.
  • The intracellular localization of p33/gC1qR prevents its interaction with extracellular C1q.
  • The proposed function of p33/gC1qR as a cell surface C1q receptor requires reconsideration based on its mitochondrial localization.

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