title: A role for Rab7 in the movement of secretory granules in cytotoxic T lymphocytes.
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.
authors: Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 0XY, UK.
authors: Tiziana
authors: T
authors: Daniele
authors: Yvonne
authors: Y
authors: Hackmann
authors: Alex T
authors: AT
authors: Ritter
authors: Matt
authors: M
authors: Wenham
authors: Sarah
authors: S
authors: Booth
authors: Giovanna
authors: G
authors: Bossi
authors: Michael
authors: M
authors: Schintler
authors: Michaela
authors: M
authors: Auer-Grumbach
authors: Gillian M
authors: GM
authors: Griffiths
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins; D009154:Mutation; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109571:BICD1 protein, human; C561542:BICD2 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; C423317:RILP protein, human; D011993:Recombinant Fusion Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D006160:Guanosine Triphosphate; D004398:Dyneins; D020691:rab GTP-Binding Proteins