title: Preparing the lethal hit: interplay between exo- and endocytic pathways in cytotoxic T lymphocytes.
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.
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Hsin-Fang
authors: HF
authors: Chang
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Hawraa
authors: H
authors: Bzeih
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Praneeth
authors: P
authors: Chitirala
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Keerthana
authors: K
authors: Ravichandran
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Marwa
authors: M
authors: Sleiman
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Elmar
authors: E
authors: Krause
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Ulrike
authors: U
authors: Hahn
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany.
authors: Varsha
authors: V
authors: Pattu
authors: Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421, Homburg, Germany. jrettig@uks.eu.
authors: Jens
authors: 0000-0001-6160-3954
authors: J
authors: Rettig
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology; D005089:Exocytosis; D006801:Humans; D008247:Lysosomes / Q000276:immunology; D008561:Membrane Fusion; D050600:SNARE Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*
chemical_list: D050600:SNARE Proteins
keywords: Correlative light and electron microscopy; Early endosomes; Late endosomes; Recycling endosomes; SNARE proteins; Total internal reflection fluorescence microscopy