A Truncated Splice-Variant of the Fc epsilon RI beta Receptor Subunit Is Critical for Microtubule Formation and Degranulation in Mast Cells

作者：Cruse Glenn^*; Beaven Michael A; Ashmole Ian; Bradding Peter; Gilfillan Alasdair M; Metcalfe Dean D

来源：Immunity, 2013, 38(5): 906-917.

DOI：10.1016/j.immuni.2013.04.007

Human linkage analyses have implicated the MS4A2-containing gene locus (encoding Fc epsilon RI beta) as a candidate for allergy susceptibility. We have identified a truncation of Fc epsilon RI beta (t-Fc epsilon RI beta) in humans that contains a putative calmodulin-binding domain and thus, we sought to identify the role of this variant in mast cell function. We determined that t-Fc epsilon RI beta is critical for microtubule formation and degranulation and that it may perform this function by trafficking adaptor molecules and kinases to the pericentrosomal and Golgi region in response to Ca2+ signals. Mutagenesis studies suggest that calmodulin binding to t-Fc epsilon RI beta in the presence of Ca2+ could be critical for t-Fc epsilon RI beta function. In addition, gene targeting of t-Fc epsilon RI beta attenuated microtubule formation, degranulation, and IL-8 production downstream of Ca2+ signals. Therefore, t-Fc epsilon RI beta mediates Ca2+-dependent microtubule formation, which promotes degranulation and cytokine release. Because t-Fc epsilon RI beta has this critical function, it represents a therapeutic target for the downregulation of allergic inflammation.

• 出版日期2013-5-23