A role for Rab7 in the movement of secretory granules in cytotoxic T lymphocytes |
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Authors: | Daniele Tiziana Hackmann Yvonne Ritter Alex T Wenham Matt Booth Sarah Bossi Giovanna Schintler Michael Auer-Grumbach Michaela Griffiths Gillian M |
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Affiliation: | Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 0XY, UK. |
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Abstract: | 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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Keywords: | Bicaudal CTL CMT2B dynein lymphocytes lysosomes ORP1L polarization Rab7 RILP secretion |
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