Biosynthesis and sorting of myeloperoxidase in hematopoietic cells.
The neutrophil granulocytes have a critical role in innate immunity through killing of phagocytized microorganisms, in which myeloperoxidase (MPO) participates. MPO is stored in cytoplasmic azurophil lysosome-like granules together with other antibiotic proteins and digestive enzymes. During passage in the secretory pathway pro-MPO is folded, subjected to oligosaccharide modification, and retrieval from constitutive secretion to become targeted to azurophil granules for final processing and storage. Propeptide-deleted MPO precursor was found not to be processed to mature MPO and not to be targeted for storage but instead degraded or secreted. This indicated that the propeptide of the MPO precursor was a prerequisite for the final processing and granule targeting of proMPO. When the MPO propeptide was expressed as a chimera with a normally secretory protein, the ER retention of the chimera was prolonged compared with that of the native protein. Thus, the propeptide of MPO precursor may also mediate the normally long ER-residence of proMPO. Both mature MPO and secreted proMPO contained complex oligosaccharide side chains indicating that proMPO and, thus, mature MPO has passed the medial Golgi stack where complex oligosaccharides are formed, and exited at TGN like other proteins targeted for azurophil granules.
Olsson
Inge
I
Department of Hematology, Lund University, Lund, Sweden. Inge.Olsson@hematogi.lu.se
Bulow
Elinor
E
Hansson
Markus
M
D000818:Animals; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells; D006801:Humans; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D015398:Signal Transduction
D004792:Enzyme Precursors; D009195:Peroxidase