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Journal of Molecular Medicine

, Volume 82, Issue 7, pp 423–433 | Cite as

Autoantigens of the nuclear pore complex

  • P. Enarson
  • J. B. Rattner
  • Y. Ou
  • K. Miyachi
  • T. Horigome
  • M. J. FritzlerEmail author
Review

Abstract

The nuclear envelope (NE) is one of many intracellular targets of the autoimmune response in patients with autoimmune liver disease, systemic lupus erythematosus, and related conditions. In eukaryotic organisms the NE consists of five interconnected regions: an outer nuclear membrane (ONM) that is continuous with the endoplasmic reticulum, an intermembrane or perinuclear space, an inner nuclear membrane (INM) with a unique set of integral membrane proteins, the underlying nuclear lamina, and the pore domains that are regions where the ONM and INM come together. The pore domains are sites of regulated continuity between the cytoplasm and nucleus that are occupied by supramolecular structures, termed nuclear pore complexes (NPCs). Human autoantibodies identified to date bind to specific components in three of the five NE compartments. Autoantigen targets include the lamins A, B, and C of the nuclear lamina, gp210, p62 complex proteins, Nup153, and Tpr within the NPC, and LBR, MAN1, LAP1, and LAP2 that are integral proteins of the INM. Autoantibodies to these NE targets have been shown to be correlated with various autoimmune diseases such as primary biliary cirrhosis, other autoimmune liver diseases and systemic rheumatic diseases. Now that the proteome of the NE is more clearly defined, other autoantibodies to components in this cell compartment are likely to be defined.

Keywords

Nuclear envelope Nuclear pore complex Autoantibodies Autoimmune diseases Antigens 

Abbreviations

NE

Nuclear envelope

ONM

Outer nuclear membrane

INM

Inner nuclear membrane

NPC

Nuclear pore complex

IIF

Indirect immunofluorescence

SLE

Systemic lupus erythematosus

PBC

Primary biliary cirrhosis

CFS

Chronic fatigue syndrome

Notes

Acknowledgements

The authors extend appreciation to Meifeng Zhang for producing some of the illustrations, and to Drs. N. Pante and I. Macara for permission to use previously published graphics. This research was supported by the Canadian Institutes of Health Research (grant no. MOP 38034) and a grant from the Natural Sciences and Environment Research Council to J.B.R. M.J.F. holds the Arthritis Society Research Chair at the University of Calgary. P.E. was supported by an MD/PhD studentship from the Alberta Heritage Foundation for Medical Research, and Y.O. is supported by a CIHR/Ernst & Young Post-doctoral Award.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • P. Enarson
    • 1
  • J. B. Rattner
    • 1
  • Y. Ou
    • 1
  • K. Miyachi
    • 2
  • T. Horigome
    • 3
  • M. J. Fritzler
    • 4
    Email author
  1. 1.Department of Anatomy and Cell Biology, Faculty of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.Health Sciences Research InstituteKanagawaJapan
  3. 3.Department of Chemistry, Faculty of SciencesNiigata UniversityNiigataJapan
  4. 4.Department of Medicine, Faculty of MedicineUniversity of CalgaryCalgaryCanada

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