Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Immunol. 2016 Sep 15;197(6):2473-84. doi: 10.4049/jimmunol.1600828. Epub 2016 Aug 15.

Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes.

Author information

1
Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg/Saar, Germany; and.
2
Department of Physiology, University of Alberta, Edmonton T6G 2H7, Alberta, Canada.
3
Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg/Saar, Germany; and jrettig@uks.eu Varsha.Pattu@uks.eu.

Abstract

CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process.

PMID:
27527597
DOI:
10.4049/jimmunol.1600828
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center