SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast cell line

SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast cell line
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DOI:
10.1016/s0161-5890(02)00085-8
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发表时间:
2002-09-01
影响因子:
3.6
通讯作者:
Varin-Blank, N
Varin-Blank, N
中科院分区:
医学3区
文献类型:
--
作者:
Blank, U;Cyprien, B;Varin-Blank, N

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肥大细胞通过释放储存在大量细胞质颗粒中的生物活性介质参与炎症和过敏。脱粒受到严格控制,需要激活细胞表面受体,如高亲和力IgE受体(Fc ε RI)。在这里,我们讨论了一些关键组成部分的分子机制,调节颗粒和质膜之间的融合的最后步骤的基础上获得的结果与大鼠肥大细胞系RBL-2 H3。我们强调可溶性N-乙基马来酰亚胺附着蛋白受体(SNARE)蛋白的作用,如突触融合蛋白4,可以通过与SNAP-23形成稳定的复合物来促进膜融合。我们还强调了Ser/Thr激酶的作用,发现与Rab 3D相关,Rab 3D是一种脱粒的负调节因子。相关的激酶活性在刺激后由于细胞内钙增加而减少,特异性磷酸化突触融合蛋白4,从而影响其与其t-SNARE伴侣SNAP-23结合的能力。我们的研究结果提出了一种新的方式Rab 3 GTP酶可能与被认为是膜融合的通用介质的SNARE的功能相交。(C)2002爱思唯尔科技有限公司。保留所有权利。
Mast cells participate in inflammation and allergies by releasing biologically active mediators stored in numerous cytoplasmic granules. Degranulation is tightly controlled and requires activation of cell surface receptors, such as the high affinity IgE receptor (FcepsilonRI). Here, we discuss some of the key components of the molecular machinery that regulates the final steps of fusion between the granular and plasma membrane based on results obtained with the rat mast cell line RBL-2H3. We emphasize the role of soluble N-ethylmaleimide attachment protein receptors (SNAREs) proteins such as syntaxin 4 that can promote membrane fusion through formation of a stable complex with SNAP-23. We also highlight the role of a Ser/Thr kinase found to be associated with Rab3D, a negative regulator of degranulation. Associated kinase activity, which diminishes after stimulation as a consequence of intracellular calcium increases, specifically phosphorylates syntaxin 4 thereby affecting its capacity to bind to its t-SNARE partner SNAP-23. Our results suggest a new way of how Rab3 GTPases may intersect with the function of SNAREs thought to be universal mediators of membrane fusion. (C) 2002 Elsevier Science Ltd. All rights reserved.