Phosphorylation of SNAP-23 by IkB kinase 2 regulates mast cell degranulation (Cell, 2008, 134:485-495)

報告日期: 2008/10/21
報告時間: 15:10/46:00
報告學生: 林嬿琳
講評老師: 謝奇璋
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971021-1.pdf

Phosphorylation of SNAP-23 by IkB Kinase 2 Regulates Mast Cell Degranulation

Cell 134,485-95 (2008)

Speaker: 林嬿琳

Commentator: 謝奇璋老師

Time:15:10-16:00, Oct.21, 2008

Place: Room 602

 

Abstract:

  Type I hypersensitivity is mainly mediated by mast cells. Once antigens cross-links with antigen-specific immunoglobulin E (IgE) bound to high affinity FceRI receptor-bearing mast cells, they are activated to degranulate and release their preformed mediators from granules such as histamine which can increase vascular permeability. Then, TNF-a and IL-6 are synthesized and secreted to promote late-phase allergic reactions. However, the precise mechanism controlling the responses of mast cells has been unclear. Previous studies have shown that NF-kB activation induced by Bcl10-Malt1 complex is indispensible for TNF-a production by

mast cells. But whether IkB Kinase 2(IKK2) participates in IgE-mediated responses of mast cells needs further to be investigated. Therefore, the author adoptively transfered IL-3 in vitro differentiated fetal liver-derived mast cells (FLMCs) from wild-type or IKK2-/- embryos into mast cell deficient mice. After intradermally sensitized with monoclonal mouse dinitrophenol-specific (anti-DNP) IgE and intravenously challenged with DNP, anaphylactic reactions was impaired in IKK2-/- FLMC-reconstituted mice due to dysfunctional degranulation. For mast cells, it has been reported that synaptosome-associated protein of 23 kDa (SNAP23) is responsible for membrane fusion between granule membrane and plasma membrane to facilitate degranulation. The author found upon stimulation, IKK2 was recruited to lipid rafts and colocalized with and phosphorylated SNAP23 on Ser95 and Ser120, not NF-kB, to promote degranulation. In addition, TNF-a production depended on NF-kB activation by IKK2. Based on these results, IKK2 might play important roles on regulating IgE-dependent anaphylactic responses in vivo.

 

References:

1.   Suzuki, K., and Verma, I, M. 2008. Phosphorylation of SNAP-23 by IB kinase 2 regulates mast cell degranulation. Cell. 134:485-95.

2.   Klemm, S. et al. 2006. The Bcl10-Malt1 complex segregates FcRI-mediated nuclear factor B activation and cytokine production from mast cell degranulation, J. Exp. Med. 203: 337–347.