PMID- 21438968
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20151119
IS  - 1600-0854 (Electronic)
IS  - 1398-9219 (Linking)
VI  - 12
IP  - 7
DP  - 2011 Jul
TI  - Syntaxin7 is required for lytic granule release from cytotoxic T lymphocytes.
PG  - 890-901
LID - 10.1111/j.1600-0854.2011.01193.x [doi]
AB  - SNARE proteins are essential fusion mediators for many intracellular trafficking 
      events. Here, we investigate the role of Syntaxin7 (Stx7) in the release of lytic 
      granules from cytotoxic T lymphocytes (CTLs). We show that Stx7 is expressed in 
      CTLs and is preferentially localized to the region of lytic granule release, the 
      immunological synapse (IS). Interference of Stx7 function by expression of a 
      dominant-negative Stx7 construct or by small interfering RNA leads to a dramatic 
      reduction of CTL-mediated killing of target cells. Real-time visualization of 
      individual lytic granules at the IS by evanescent wave microscopy reveals that 
      lytic granules in Stx7-deprived CTLs not only fail to fuse with the plasma 
      membrane but even fail to accumulate at the IS. Surprisingly, the accumulation 
      defect is not caused by an overall reduction in lytic granule number, but by a 
      defect in the trafficking of T cell receptors (TCRs) through endosomes. 
      Subsequent high-resolution nanoscopy shows that Stx7 colocalizes with Rab7 on 
      late endosomes. We conclude from these data that the accumulation of recycling 
      TCRs at the IS is a SNARE-dependent process and that Stx7-mediated processing of 
      recycling TCRs through endosomes is a prerequisite for the cytolytic function of 
      CTLs.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Pattu, Varsha
AU  - Pattu V
AD  - Institut fur Physiologie, Universitat des Saarlandes, Kirrberger Strasse 8, 
      Gebaude 59, 66421 Homburg, Saarland, Germany.
FAU - Qu, Bin
AU  - Qu B
FAU - Marshall, Misty
AU  - Marshall M
FAU - Becherer, Ute
AU  - Becherer U
FAU - Junker, Christian
AU  - Junker C
FAU - Matti, Ulf
AU  - Matti U
FAU - Schwarz, Eva C
AU  - Schwarz EC
FAU - Krause, Elmar
AU  - Krause E
FAU - Hoth, Markus
AU  - Hoth M
FAU - Rettig, Jens
AU  - Rettig J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110421
PL  - England
TA  - Traffic
JT  - Traffic (Copenhagen, Denmark)
JID - 100939340
RN  - 0 (Biomarkers)
RN  - 0 (Qa-SNARE Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Biomarkers/metabolism
MH  - CD8-Positive T-Lymphocytes/cytology/immunology
MH  - Cytoplasmic Granules/*metabolism
MH  - Endosomes/metabolism
MH  - Exocytosis/immunology/*physiology
MH  - Humans
MH  - Immunological Synapses/physiology
MH  - Lymphocyte Activation
MH  - Membrane Fusion/physiology
MH  - Qa-SNARE Proteins/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - T-Lymphocytes, Cytotoxic/cytology/*metabolism
EDAT- 2011/03/29 06:00
MHDA- 2011/10/08 06:00
CRDT- 2011/03/29 06:00
PHST- 2011/03/29 06:00 [entrez]
PHST- 2011/03/29 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
AID - 10.1111/j.1600-0854.2011.01193.x [doi]
PST - ppublish
SO  - Traffic. 2011 Jul;12(7):890-901. doi: 10.1111/j.1600-0854.2011.01193.x. Epub 2011 
      Apr 21.