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A Role for Rab7 in the Movement of Secretory Granules in Cytotoxic T Lymphocytes
Author(s) -
Daniele Tiziana,
Hackmann Yvonne,
Ritter Alex T.,
Wenham Matt,
Booth Sarah,
Bossi Giovanna,
Schintler Michael,
AuerGrumbach Michaela,
Griffiths Gillian M.
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01194.x
Subject(s) - microbiology and biotechnology , biology , ctl* , centrosome , cytotoxic t cell , rab , secretion , lysosome , immunological synapse , endosome , dynein , secretory pathway , microtubule , gtpase , immunology , cell , immune system , golgi apparatus , t cell , intracellular , biochemistry , enzyme , t cell receptor , endoplasmic reticulum , cell cycle , in vitro
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.