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Cell Mol Life Sci. 2017 Feb;74(3):399-408. doi: 10.1007/s00018-016-2350-7. Epub 2016 Sep 1.

Preparing the lethal hit: interplay between exo- and endocytic pathways in cytotoxic T lymphocytes.

Author information

1
Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
2
Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany. jrettig@uks.eu.

Abstract

Cytotoxic T lymphocytes patrol our body in search for infected cells which they kill through the release of cytotoxic substances contained in cytotoxic granules. The fusion of cytotoxic granules occurs at a specially formed contact site, the immunological synapse, and is tightly controlled to ensure specificity. In this review, we discuss the contribution of two intracellular compartments, endosomes and cytotoxic granules, to the formation, function and disassembly of the immunological synapse. We highlight a recently proposed sequential process of fusion events at the IS upon target cell recognition. First, recycling endosomes fuse with the plasma membrane to deliver cargo required for the docking of cytotoxic granules. Second, cytotoxic granules arrive and fuse upon docking in a SNARE-dependent manner. Following fusion, membrane components of the cytotoxic granule are retrieved through endocytosis to ensure the fast, efficient serial killing of target cells that is characteristic of cytotoxic T lymphocytes.

KEYWORDS:

Correlative light and electron microscopy; Early endosomes; Late endosomes; Recycling endosomes; SNARE proteins; Total internal reflection fluorescence microscopy

PMID:
27585956
PMCID:
PMC5241346
DOI:
10.1007/s00018-016-2350-7
[Indexed for MEDLINE]
Free PMC Article

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