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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Immature T-cell clustering and efficient differentiation require the polarity protein Scribble
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Immature T-cell clustering and efficient differentiation require the polarity protein Scribble

机译：未成熟的T细胞聚集和有效分化需要极性蛋白涂抹

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摘要

T-cell polarization is required for cell migration and cell-cell interactions, cellular behaviors crucial for lymphocyte differentiation. Despite expression of the epithelial polarity network in T cells, neither its contribution to thymocyte polarity nor its requirement during development is known. We report here that depletion of the polarity protein Scribble in hematopoietic progenitor cells results in inefficient T-cell development characterized by a partial developmental block during the early double-negative (DN) stage of differentiation. Scribble-depleted hematopoietic progenitor cells exhibit a delayed transition into late CD44~(lo/-)CD25~+ DN3 cells, evidenced by the accumulation of early CD44~(int)CD25~+ DN3 cells. As a consequence, a limited cellular expansion and a reduced frequency of intracellular T-cell receptor β-positive DN3 cells are observed among Scribble-deficient differentiating T cells. Moreover, whereas purified Scribble-depleted DN2 and DN3 cells do not exhibit compromised spontaneous motility, T-cell clustering and prolonged homotypic interactions among such cells are reduced. This deficiency correlates with a lack of polarization of the integrin LFA-1 during T-cell migration or on the initiation of T-cell-T-cell interactions. Scribble is therefore a critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression.
机译：T细胞极化对于细胞迁移和细胞间相互作用是必需的，细胞行为对于淋巴细胞分化至关重要。尽管在T细胞中表达了上皮极性网络，但尚不清楚其对胸腺细胞极性的贡献或在发育过程中的需求。我们在此报告，造血祖细胞中极性蛋白Scribble的耗竭导致低效率的T细胞发育，其特征在于分化的早期双阴性（DN）阶段的部分发育受阻。杂草枯竭的造血祖细胞表现出向晚期CD44〜（lo /-）CD25〜+ DN3细胞的过渡延迟，这由早期CD44〜（int）CD25〜+ DN3细胞的积累所证明。结果，在杂乱缺陷的分化T细胞中观察到有限的细胞扩增和胞内T细胞受体β阳性DN3细胞的频率降低。而且，尽管纯化的无杂物的DN2和DN3细胞没有表现出自发的运动能力受损，但这种细胞之间的T细胞簇集和同型相互作用延长了。这种缺陷与在T细胞迁移过程中或在T细胞与T细胞相互作用开始时缺乏整联蛋白LFA-1的极化有关。因此，涂鸦是导致未成熟T细胞聚集的关键因素，此处显示的事件对于有效的发育进程是必需的。

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    Kelly A. Pike; Sarang Kulkarni; Tony Pawson;

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    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;

    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;

    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5,Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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