A role for Rab7 in the movement of secretory granules in cytotoxic T lymphocytes.

A role for Rab7 in the movement of secretory granules in cytotoxic T lymphocytes.
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Rab7在分泌颗粒在细胞毒性T淋巴细胞中的运动中的作用。

DOI:
10.1111/j.1600-0854.2011.01194.x
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发表时间:
2011-07
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Griffiths GM
Griffiths GM
中科院分区:
其他
文献类型:
--
作者:
Daniele T;Hackmann Y;Ritter AT;Wenham M;Booth S;Bossi G;Schintler M;Auer-Grumbach M;Griffiths GM

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细胞毒性T淋巴细胞(CTL)是病毒感染和致瘤细胞的强效杀手。在识别靶细胞后,CTL在CTL和靶细胞之间形成的免疫突触(IS)经历分泌性溶酶体的极化分泌。然而,涉及分泌型溶酶体极化的分子机制在很大程度上仍不清楚。在本文中,我们研究了Rab7在分泌型溶酶体极化中的作用。我们表明,通过RNA干扰沉默Rab7降低了CTL杀伤目标的能力。GTP结合的Rab7和Rab相互作用的溶酶体蛋白RILP相互作用,并都定位于CTL中的分泌型溶酶体。RILP的过度表达会将动力蛋白招募到分泌型溶酶体的膜上,并触发它们向中心体移动。综上所述,这些结果表明,Rab7可能通过与RILP相互作用招募负端运动Dynein,在溶酶体向中心体的分泌性移动中发挥作用。
Cytotoxic T lymphocytes (CTL) are potent killers of virally infected and tumorigenic cells. Upon recognition of target cells, CTL undergo polarized secretion of secretory lysosomes at the immunological synapse (IS) that forms between CTL and target. However, the molecular machinery involved in the polarization of secretory lysosomes is still largely uncharacterized. In this paper, we investigated the role of Rab7 in the polarization of secretory lysosomes. We show that silencing of Rab7 by RNA interference reduces the ability of CTL to kill targets. GTP-bound Rab7 and Rab interacting lysosomal protein, RILP, interact and both localize to secretory lysosomes in CTL. Over-expression of RILP recruits dynein to the membranes of secretory lysosomes and triggers their movement toward the centrosome. Together, these results suggest that Rab7 may play a role in secretory lysosome movement toward the centrosome by interacting with RILP to recruit the minus-end motor, dynein.
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