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Related Experiment Videos

Evidence for a second alpha 2-macroglobulin receptor

U K Misra1, C T Chu, G Gawdi

  • 1Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.

The Journal of Biological Chemistry
|April 29, 1994
PubMed
Summary
This summary is machine-generated.

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Macrophages possess a second alpha 2-macroglobulin (alpha 2M) receptor, distinct from LRP, which is G protein-coupled. This receptor mediates signaling pathways involving calcium and inositol phosphates.

Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • Alpha 2-macroglobulin (alpha 2M) binding to macrophage receptors influences intracellular signaling.
  • Low density lipoprotein receptor-related protein (LRP) is hypothesized to be the primary alpha 2M receptor.
  • The existence of a distinct alpha 2M signaling receptor in macrophages remains to be fully elucidated.

Purpose of the Study:

  • To investigate the signal transduction mechanisms initiated by alpha 2M-methylamine and its receptor interactions in macrophages.
  • To determine if the known LRP/alpha 2M receptor-associated protein (RAP) affects alpha 2M-mediated signaling.
  • To characterize the nature of the G protein coupling involved in alpha 2M-induced macrophage activation.

Main Methods:

  • Utilized human alpha 2M-methylamine and recombinant receptor binding fragment (RBF) to stimulate macrophages.

Related Experiment Videos

  • Measured intracellular calcium ([Ca2+]i) and inositol 1,4,5-triphosphate levels in response to ligands.
  • Investigated the role of RAP by pre-treating macrophages, and employed GTP gamma S and GDP beta S in permeabilized cells to probe G protein involvement.

    • Main Results:

    • Both alpha 2M-methylamine and RBF induced a rapid increase in intracellular calcium ([Ca2+]i).
    • Receptor-associated protein (RAP) did not inhibit the calcium response, suggesting a distinct binding site for alpha 2M.
    • RBF stimulated inositol 1,4,5-triphosphate production, which was potentiated by GTP gamma S and abrogated by GDP beta S, indicating G protein coupling.

    Conclusions:

    • Macrophages possess a second alpha 2M receptor, separate from LRP, that mediates signaling.
    • This novel alpha 2M receptor is coupled to a pertussis toxin-insensitive and potentially cholera toxin-sensitive G protein.
    • The findings reveal a new G protein-coupled receptor pathway for alpha 2M in macrophages.