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Endoplasmic reticulum aminopeptidases: biology and pathogenic potential

Nature Reviews Rheumatology volume 6, pages 461–467 (2010)Cite this article

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Abstract

Endoplasmic reticulum aminopeptidase 1 (ERAP1) and the closely related ERAP2 are involved in the final trimming of peptides within the endoplasmic reticulum for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 was found to be associated with ankylosing spondylitis (AS) in a genome-wide association study of nonsynonymous single nucleotide polymorphisms, and this association has been confirmed in several studies. An ERAP1/ERAP2 haplotype has also been reported to be associated with familial AS. ERAP1 and ERAP2 could carry out several potential roles in the pathogenesis of AS. ERAP1-deficient mice show a considerable alteration in the level and repertoire of peptides presented by MHC class I molecules. Furthermore, ERAP1 has been shown to be involved in shedding cytokine receptors. Both of these functions require further analysis to better understand the exact role of ERAP1 in AS.

Key Points

  • An association between the genes encoding endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 and ankylosing spondylitis (AS) has been identified

  • ERAP1 and ERAP2 act in concert to trim and present peptides on major histocompatibility complex class I molecules within the endoplasmic reticulum

  • ERAP1 is also known to aid in the shedding of membrane-bound cytokine receptors

  • Preliminary data suggest that the peptide-trimming functions of ERAP1 and ERAP2 might be important in the pathogenesis of AS

  • Determining the crystallographic structure of ERAP1 should help greatly in the study of the function of this molecule

  • Large cohort studies looking at the clinical relevance of the association between ERAP1 and AS could shed more light on this novel and promising lead

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Figure 1: ERAP and MHC class-I peptide presentation.

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  1. Division of Rheumatology, Toronto Western Hospital, 399 Bathurst Street, M5T 2S8, Toronto, ON, Canada

    Nigil Haroon & Robert D. Inman

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Haroon, N., Inman, R. Endoplasmic reticulum aminopeptidases: biology and pathogenic potential. Nat Rev Rheumatol 6, 461–467 (2010). https://doi.org/10.1038/nrrheum.2010.85

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