4.7 Review

Calreticulin: non-endoplasmic reticulum functions in physiology and disease

Journal

FASEB JOURNAL
Volume 24, Issue 3, Pages 665-683

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.09-145482

Keywords

phagocytosis; migration; extracellular matrix; wound healing; tumor recognition

Funding

  1. U.S. National Institutes of Health (NIH) [HL079644, T32 HL07918]
  2. Medical Scientist Training Program [T32 GM008361]
  3. American Red Cross [ARC17231, 16537]
  4. European Union [FP7 215009]
  5. Calretex, Inc., LLC
  6. Canadian Institutes of Health Research [MOP-15291]
  7. New York University Summer Fellowship in Internal Medicine
  8. National Center for Research Resources [C06 RR 15490]
  9. NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015490] Funding Source: NIH RePORTER
  10. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL079644, T32HL007918] Funding Source: NIH RePORTER
  11. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008361] Funding Source: NIH RePORTER

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Calreticulin (CRT), when localized to the endoplasmic reticulum (ER), has important functions in directing proper conformation of proteins and glycoproteins, as well as in homeostatic control of cytosolic and ER calcium levels. There is also steadily accumulating evidence for diverse roles for CRT localized outside the ER, including data suggesting important roles for CRT localized to the outer cell surface of a variety of cell types, in the cytosol, and in the extracellular matrix (ECM). Furthermore, the addition of exogenous CRT rescues numerous CRT-driven functions, such as adhesion, migration, phagocytosis, and immunoregulatory functions of CRT-null cells. Recent studies show that topically applied CRT has diverse and profound biological effects that enhance cutaneous wound healing in animal models. This evidence for extracellular bioactivities of CRT has provided new insights into this classically ER-resident protein, despite a lack of knowledge of how CRT exits from the ER to the cell surface or how it is released into the extracellular milieu. Nonetheless, it has become clear that CRT is a multicompartmental protein that regulates a wide array of cellular responses important in physiological and pathological processes, such as wound healing, the immune response, fibrosis, and cancer.-Gold, L. I., Eggleton, P., Sweetwyne, M. T., Van Duyn, L. B., Greives, M. R., Naylor, S.-M., Michalak, M., Murphy-Ullrich, J. E. Calreticulin: non-endoplamic reticulum functions in physiology and disease. FASEB J. 24, 665-683 (2010). www.fasebj.org

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