Activation-induced endocytosis of the raft-associated transmembrane adaptor protein LAB/NTAL in B lymphocytes: evidence for a role in internalization of the B cell receptor.
Activation-induced endocytosis of the raft-associated transmembrane adaptor protein LAB/NTAL in B lymphocytes: evidence for a role in internalization of the B cell receptor.
复制标题
B 淋巴细胞中筏相关跨膜接头蛋白 LAB/NTAL 的激活诱导内吞作用：B 细胞受体内化作用的证据。
DOI：
10.1093/intimm/dxl118
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发表时间：
2007
影响因子：
4.4
通讯作者：
Deans,JulieP
中科院分区：
文献类型：
--
作者：
Mutch,CathlinM;Sanyal,Ratna;Unruh,TammyL;Grigoriou,Lana;Zhu,Minghua;Zhang,Weiguo;Deans,JulieP
B细胞活化连接子（LAB）/非T细胞活化连接子（NTAL）和与富含糖磷脂的膜微区相关的磷蛋白（PAG）/Csk结合蛋白（Cbp）是在受体信号传导途径的即时/早期阶段具有不同功能的筏相关跨膜衔接蛋白。异质性筏被认为是划分膜相关的信号事件。为了研究LAB/NTAL和PAG/Cbp的亚细胞定位，在人B细胞系中将它们表达为荧光嵌合融合蛋白，并在B细胞受体（BCR）刺激之前和之后检查它们的分布沿着相应的内源性蛋白。这两个适配器主要分布在质膜上的静息细胞和其他筏相关的蛋白质共簇，然而，他们分布不同的浮力膜分离的洗涤剂抗性或非洗涤剂的方法，表明他们可能本地化到不同的筏。活化后，LAB/NTAL被内化并与BCR共定位，而PAG/Cbp保留在细胞表面。在LAB/NTAL缺陷的小鼠B细胞中，BCR内化减少，表明LAB/NTAL在活化诱导的BCR内化中具有调节作用。LAB/NTAL的胞质结构域，而不是跨膜/质膜区域，被认为是其内化所必需的。
Linker for activation of B cell (LAB)/non-T cell activation linker (NTAL) and phosphoprotein associated with glycophospholipid-enriched membrane microdomain (PAG)/Csk-binding protein (Cbp) are raft-associated transmembrane adaptor proteins with distinct functions in immediate/early phases of receptor signaling pathways. Heterogeneous rafts are thought to compartmentalize membrane-associated signaling events. In order to investigate the subcellular localization of LAB/NTAL and PAG/Cbp, they were expressed as fluorescent chimeric fusion proteins in a human B cell line and their distribution was examined, along with the corresponding endogenous proteins, before and after B cell receptor (BCR) stimulation. Both adaptors were distributed predominantly at the plasma membrane in resting cells and co-clustered with other raft-associated proteins; however, they distributed differently in buoyant membranes isolated by either detergent resistance or non-detergent methods, indicating that they might localize to distinct rafts. After activation, LAB/NTAL was internalized and co-localized with the BCR while PAG/Cbp remained on the cell surface. BCR internalization was reduced in LAB/NTAL-deficient murine B cells, suggesting a regulatory role for LAB/NTAL in activation-induced internalization of the BCR. The cytoplasmic domain of LAB/NTAL, and not the transmembrane/juxtamembrane region, was found to be essential for its internalization.