VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity.
Bottom Line: Although multiple SNARE proteins have been implicated in cytotoxic granule exocytosis, the role of vesicular SNARE proteins, i.e., vesicle-associated membrane proteins (VAMPs), remains enigmatic.In primary human CTLs, however, VAMP8 colocalized with Rab11a-positive recycling endosomes.Our findings imply that secretory granule exocytosis pathways in other cell types may also be more complex than previously appreciated.
Affiliation: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany Department of Medicine, Center For Infectious Medicine, 14186 Stockholm, Sweden.Show MeSH
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Mentions: We set out to decipher how VAMP8 may facilitate cytotoxic granule exocytosis. In contrast to studies of mouse CTL (Loo et al., 2009), we found VAMP8 localization to be distinct from that of granzyme B in unconjugated, fixed human primary CTLs using SIM (Fig. 2 A). Of note, VAMP8-carrying compartments were more numerous than those with granzyme B. Upon conjugation with SEA-pulsed target cells, VAMP8-carrying vesicles did not start to colocalize with those containing granzyme B (Fig. 2 B). Similarly, VAMP8-carrying vesicles did not colocalize with perforin-containing vesicles in unconjugated or conjugated CTLs (Fig. 2, C and D). Unexpectedly, we conclude that VAMP8 localized to a compartment distinct from cytotoxic granules in human CTLs.
Affiliation: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany Department of Medicine, Center For Infectious Medicine, 14186 Stockholm, Sweden.