Adapters in the organization of mast cell signaling

Authors

  • Damiana Alvarez-Errico,

    1. Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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    • *

      Authors contributed equally.

  • Eva Lessmann,

    1. Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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    • *

      Authors contributed equally.

  • Juan Rivera

    1. Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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Juan Rivera
Laboratory of Molecular Immunogenetics
NIAMS, NIH
Building 10, Room 13C103, MSC1930
10 Center Drive
Bethesda, MD 20892-1930, USA
Tel.: +1 301 496 7592
Fax: +1 301 480 1580
e-mail: juan-rivera@nih.gov

Abstract

Summary:  Mast cells are pivotal in innate immunity and play an important role in amplifying adaptive immunity. Nonetheless, they have long been known to be central to the initiation of allergic disorders. This results from the dysregulation of the immune response whereby normally innocuous substances are recognized as non-self, resulting in the production of IgE antibodies to these ‘allergens’. Preformed and newly synthesized inflammatory (allergic) mediators are released from the mast cell following allergen-mediated aggregation of allergen-specific IgE bound to the high-affinity receptors for IgE (FcεRI). Thus, the process by which the mast cell is able to interpret the engagement of FcεRI into the molecular events necessary for release of their allergic mediators is of considerable therapeutic interest. Unraveling these molecular events has led to the discovery of a functional class of proteins that are essential in organizing activated signaling molecules and in coordinating and compartmentalizing their activity. These so-called ‘adapters’ bind multiple signaling proteins and localize them to specific cellular compartments, such as the plasma membrane. This organization is essential for normal mast cell responses. Here, we summarize the role of adapter proteins in mast cells focusing on the most recent advances toward understanding how these molecules work upon FcεRI engagement.

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