A Role for Rab7 in the Movement of Secretory Granules in Cytotoxic T Lymphocytes

Abstract

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.

The Rab Interacting Lysosomal Protein (RILP) Homology Domain Functions as a Novel Effector Domain for Small GTPase Rab36

“…in lyososome transport and in retrograde mela-nosome transport, respectively, remains to be determined, the series of Rab binding-deficient mutants of RILP produced in this study is an ideal and powerful tool for determining which Rab functions together with RILP in particular membrane trafficking events, e.g. phagosome maturation (36) and lytic granule movement (37), in the future.…”

Mechanisms and functions of lysosome positioning

“…After binding to the target cells, lytic granules move towards the MTOC, which in activated CTLs becomes localized under the plasma membrane of the immune synapse (Stinchcombe et al, 2006). This retrograde movement is mediated by the Rab7-RILP-dynein ensemble (Daniele et al, 2011). The Arl8-SKIPkinesin-1 pathway, by contrast, is required to position the MTOC and lytic granules to the immune synapse in NK cells (Tuli et al, 2013).…”

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

“…This removes the dynein-dynactin components, allowing plus-end-directed transport of late endosomes. This role for Rab7 gives insight into the coupling of metabolic sensing with motor activity to regulate organelle positioning, and the same interaction network has also been implicated in the positioning of secretory granules in cytotoxic T lymphocytes (Daniele et al, 2011).…”