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Roles of Calreticulin and Calnexin in Myeloperoxidase Synthesis

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Calreticulin

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

Polymorphonuclear leukocytes (PMNs) represent the essential cellular component of acute inflammation. As such, PMNs mediate a wide array of functions critical for effective antimicrobial activity and integral for noninfectious proinflammatory events. PMNs contribute to normal host defense using cellular responses that include reactive oxygen species, an array of granule enzymes, and many directly cytotoxic antimicrobial proteins. The potency of the oxygen-dependent system is amplified by the action of myeloperoxidase (MPO), a glycosylated hemeprotein located in the PMN azurophilic granule. Under normal circumstances, MPO synthesis is restricted to the promyelocyte stage of myeloid development in the bone marrow. The molecular chaperones calreticulin, calnexin, and ERp57 each interact with normal MPO precursors during their biosynthesis in the ER. The mechanisms for these associations and the basis for their selectivity are not known. Not only do these chaperones participate in normal MPO biosynthesis, but they also contribute to “quality control”, demonstrated by their prolonged association with mutant species of MPO. However, not all MPO mutants are handled in an identical fashion, indicating that the chaperones have the capacity to be selective in their interactions. Understanding the structural basis for these interactions, both with normal and aberrant MPO species, and the functional implications of these apparently selective associations should provide important insights into the role of molecular chaperones in normal protein folding and quality control in the ER.

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  1. William M. Nauseef
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Editors and Affiliations

  1. Peninsula Medical School, Devon, U.K. MRC Immunochemistry Unit Department of Biochemistry, University of Oxford, Oxford, UK

    Paul Eggleton Ph.D.

  2. CIHR Membrane Protein Research Group Department of Biochemistry, University of Alberta Edmonton, Alberta, Canada

    Marek Michalak Ph.D.

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Nauseef, W.M. (2003). Roles of Calreticulin and Calnexin in Myeloperoxidase Synthesis. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_7

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  • DOI: https://doi.org/10.1007/978-1-4419-9258-1_7

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