The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells.
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The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells. / Herda, Stefanie; Raczkowski, Friederike; Mittrücker, Hans Willi; Willimsky, Gerald; Gerlach, Kerstin; Kühl, Anja A; Breiderhoff, Tilman; Willnow, Thomas E; Dörken, Bernd; Höpken, Uta E; Rehm, Armin.
in: IMMUNITY, Jahrgang 37, Nr. 5, 5, 2012, S. 854-866.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells.
AU - Herda, Stefanie
AU - Raczkowski, Friederike
AU - Mittrücker, Hans Willi
AU - Willimsky, Gerald
AU - Gerlach, Kerstin
AU - Kühl, Anja A
AU - Breiderhoff, Tilman
AU - Willnow, Thomas E
AU - Dörken, Bernd
AU - Höpken, Uta E
AU - Rehm, Armin
PY - 2012
Y1 - 2012
N2 - Immunological control of infections or tumors depends on the release of effector cytokines and polarized secretion of cytotoxic granules from T cells and natural killer cells. Here we show that the sorting receptor Sortilin controlled both processes. In murine Sortilin-deficient cytotoxic T lymphocytes, regulated secretion of granzyme A and cytotoxic killing was enhanced and correlated with increased vesicle-associated membrane protein 7 availability. In contrast, loss of Sortilin reduced the release of interferon-? upon infections and in autoimmune colitis. Exit of interferon-? from the Golgi apparatus required the presence of Sortilin. Furthermore, we tracked the transport route of interferon-? beyond this Sortilin-dependent Golgi to early endosome step. In wild-type T cells, trafficking of interferon-? from the endosomal sorting platform to the plasma membrane proceeded independently of recycling endosomes, and interferon-? remained excluded from late endosomes. Our results suggest that Sortilin modulates systemic immune responses through exocytic sorting of immunological effector molecules.
AB - Immunological control of infections or tumors depends on the release of effector cytokines and polarized secretion of cytotoxic granules from T cells and natural killer cells. Here we show that the sorting receptor Sortilin controlled both processes. In murine Sortilin-deficient cytotoxic T lymphocytes, regulated secretion of granzyme A and cytotoxic killing was enhanced and correlated with increased vesicle-associated membrane protein 7 availability. In contrast, loss of Sortilin reduced the release of interferon-? upon infections and in autoimmune colitis. Exit of interferon-? from the Golgi apparatus required the presence of Sortilin. Furthermore, we tracked the transport route of interferon-? beyond this Sortilin-dependent Golgi to early endosome step. In wild-type T cells, trafficking of interferon-? from the endosomal sorting platform to the plasma membrane proceeded independently of recycling endosomes, and interferon-? remained excluded from late endosomes. Our results suggest that Sortilin modulates systemic immune responses through exocytic sorting of immunological effector molecules.
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Transport
KW - T-Lymphocytes/immunology/metabolism
KW - Adaptor Proteins, Vesicular Transport/immunology/metabolism
KW - Antigens, CD4/immunology/metabolism
KW - Autoimmune Diseases/immunology/metabolism
KW - Cell Membrane/immunology/metabolism
KW - Colitis/immunology/metabolism
KW - Endosomes/immunology/metabolism
KW - Exocytosis/immunology
KW - Golgi Apparatus/immunology/metabolism
KW - Granzymes/immunology/metabolism
KW - Interferon-gamma/immunology/metabolism
KW - Interleukin-2 Receptor alpha Subunit/immunology/metabolism
KW - Killer Cells, Natural/immunology/metabolism
KW - R-SNARE Proteins/immunology/metabolism
KW - Transport Vesicles/immunology/metabolism
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Transport
KW - T-Lymphocytes/immunology/metabolism
KW - Adaptor Proteins, Vesicular Transport/immunology/metabolism
KW - Antigens, CD4/immunology/metabolism
KW - Autoimmune Diseases/immunology/metabolism
KW - Cell Membrane/immunology/metabolism
KW - Colitis/immunology/metabolism
KW - Endosomes/immunology/metabolism
KW - Exocytosis/immunology
KW - Golgi Apparatus/immunology/metabolism
KW - Granzymes/immunology/metabolism
KW - Interferon-gamma/immunology/metabolism
KW - Interleukin-2 Receptor alpha Subunit/immunology/metabolism
KW - Killer Cells, Natural/immunology/metabolism
KW - R-SNARE Proteins/immunology/metabolism
KW - Transport Vesicles/immunology/metabolism
M3 - SCORING: Journal article
VL - 37
SP - 854
EP - 866
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 5
M1 - 5
ER -
