Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells.
Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells.
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DLGH1坐标肌动蛋白聚合,突触T细胞受体和脂质筏的聚集以及T细胞中的效应子功能。
DOI:
10.1084/jem.20041428
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发表时间:
2005-02-07
影响因子:
15.3
通讯作者:
Miceli, MC
中科院分区:
文献类型:
--
作者:
Round, JL;Tomassian, T;Zhang, M;Patel, V;Schoenberger, SP;Miceli, MC
Lipid raft membrane compartmentalization and membrane-associated guanylate kinase (MAGUK) family molecular scaffolds function in establishing cell polarity and organizing signal transducers within epithelial cell junctions and neuronal synapses. Here, we elucidate a role for the MAGUK protein, Dlgh1, in polarized T cell synapse assembly and T cell function. We find that Dlgh1 translocates to the immune synapse and lipid rafts in response to T cell receptor (TCR)/CD28 engagement and that LckSH3-mediated interactions with Dlgh1 control its membrane targeting. TCR/CD28 engagement induces the formation of endogenous Lck–Dlgh1–Zap70–Wiskott-Aldrich syndrome protein (WASp) complexes in which Dlgh1 acts to facilitate interactions of Lck with Zap70 and WASp. Using small interfering RNA and overexpression approaches, we show that Dlgh1 promotes antigen-induced actin polymerization, synaptic raft and TCR clustering, nuclear factor of activated T cell activity, and cytokine production. We propose that Dlgh1 coordinates TCR/CD28-induced actin-driven T cell synapse assembly, signal transduction, and effector function. These findings highlight common molecular strategies used to regulate cell polarity, synapse assembly, and transducer organization in diverse cellular systems.
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DOI:
10.1084/jem.20030976
发表时间:
2004-01-05
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
Badour K;Zhang J;Shi F;Leng Y;Collins M;Siminovitch KA
通讯作者:
Siminovitch KA
影响因子:
56.9
作者:
Lee, KH;Holdorf, AD;Shaw, AS
通讯作者:
Shaw, AS
影响因子:
4.8
作者:
Carlier, MF;Nioche, P;Pantaloni, D
通讯作者:
Pantaloni, D
影响因子:
56.9
作者:
Dustin, ML;Colman, DR
通讯作者:
Colman, DR
影响因子:
4.8
作者:
Hanada, T;Lin, LH;Chishti, AH
通讯作者:
Chishti, AH