Studies of multimerin in human endothelial cells

Area of Science:

• Cell Biology
• Protein Biochemistry
• Vascular Biology

Background:

• Multimerin is a novel, large, soluble protein with a homomultimeric structure.
• It shares similarities with von Willebrand factor (vWF), including expression by megakaryocytes and endothelial cells.
• Both proteins are stored in platelet alpha-granules, resembling Weibel-Palade bodies.

Purpose of the Study:

• To investigate the distribution of multimerin within human endothelial cells.
• To compare the localization of multimerin with known Weibel-Palade body proteins.
• To understand the sorting mechanisms of multimerin in endothelial cells.

Main Methods:

• Immunohistochemistry on vascular endothelium in situ.
• Immunofluorescence microscopy of cultured human endothelial cells.
• Stimulation of endothelial cells with secretagogues.
• Analysis of extracellular matrix association in early passage cultures.

Main Results:

• Multimerin is present in the vascular endothelium in situ.
• In cultured endothelial cells, multimerin localizes to dense-core granules, some resembling Weibel-Palade bodies but distinct from vWF and P-selectin.
• Stimulation causes multimerin redistribution to the cell membrane without secretion.
• Multimerin associates with extracellular matrix structures differently than fibronectin.

Conclusions:

• Multimerin exhibits distinct intracellular localization in endothelial cells compared to vWF and P-selectin.
• Endothelial cells display tissue-specific sorting of multimerin and vWF.
• Multimerin undergoes regulated redistribution to the cell surface upon stimulation.