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Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion
- Source :
- Blood. 115:2674-2681
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
Abstract
- Factor XIII-A (FXIII-A) is present in the cytosol of platelets, megakaryocytes, monocytes, osteoblasts, and macrophages and may be released from cells by a nonclassical pathway. We observed that plasma FXIII-A levels were unchanged in thrombocytopenic mice (Bcl-xPlt20/Plt20 and Mpl−/−), which implicates nonclassical secretion from nucleated cells as the source of plasma FXIII-A. We, therefore, examined the intracellular targeting of FXIII-A in the THP-1 (monocyte/macrophage) cell line and in human monocyte–derived macrophages. Metabolic labeling of THP-1 cells did not show release of 35S-FXIII-A either under basal conditions or when interleukin 1-β was released in response to cell stress. However, immunofluorescence of THP-1 cells and primary macrophages showed that FXIII-A associated with podosomes and other structures adjacent to the plasma membrane, which also contain trans-Golgi network protein-46 and Golgi matrix protein-130 (GM130) but not the endoplasmic reticulum luminal protein, protein disulphide isomerase. Further, FXIII-A was present in GM130-positive intracellular vesicles that could mediate its transport, and in other contexts GM130 and its binding partner GRASP have been implicated in the delivery of nonclassically secreted proteins to the plasma membrane. Hence, this mechanism may precede FXIII-A release into the extracellular matrix from macrophages and its release into plasma from the cell type of origin.
- Subjects :
- Podosome
Interleukin-1beta
Immunology
bcl-X Protein
Golgi Apparatus
Biology
Endoplasmic Reticulum
Autoantigens
Biochemistry
Monocytes
Cell Line
Cell membrane
Mice
symbols.namesake
medicine
Animals
Macrophage
Secretion
Secretory pathway
Mice, Knockout
Organelles
Membrane Glycoproteins
Factor XIII
Macrophages
Secretory Vesicles
Monocyte
Endoplasmic reticulum
Cytoplasmic Vesicles
Membrane Proteins
Cell Biology
Hematology
Golgi apparatus
Thrombocytopenia
Cell biology
Protein Transport
medicine.anatomical_structure
symbols
Cell Surface Extensions
Receptors, Thrombopoietin
Subcellular Fractions
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....7da4d18b659f2e591120833d81fad49e