Imperial College London
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DrSophieRutschmann

Faculty of Medicine, Department of Immunology and Inflammation

Reader in Immunology
 
 
 
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Contact

 

s.rutschmann Website

 
 
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Location

 

9N4bHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Munafó:2007:10.1042/BJ20060950,
author = {Munafó, DB and Johnson, JL and Ellis, BA and Rutschmann, S and Beutler, B and Catz, SD},
doi = {10.1042/BJ20060950},
journal = {Biochem J},
pages = {229--239},
title = {Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes.},
url = {http://dx.doi.org/10.1042/BJ20060950},
volume = {402},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Neutrophils kill micro-organisms using microbicidal products that they release into the phagosome or into the extracellular space. The secretory machinery utilized by neutrophils is poorly characterized. We show that the small GTPase Rab27a is an essential component of the secretory machinery of azurophilic granules in granulocytes. Rab27a-deficient mice have impaired secretion of MPO (myeloperoxidase) into the plasma in response to lipopolysaccharide. Cell fractionation analysis revealed that Rab27a and the Rab27a effector protein JFC1/Slp1 (synaptotagmin-like protein 1) are distributed principally in the low-density fraction containing a minor population of MPO-containing granules. By immunofluorescence microscopy, we detected Rab27a and JFC1/Slp1 in a minor subpopulation of MPO-containing granules. Interference with the JFC1/Slp1-Rab27a secretory machinery impaired secretion of MPO in permeabilized neutrophils. The expression of Rab27a was dramatically increased when promyelocytic HL-60 cells were differentiated into granulocytes but not when they were differentiated into monocytes. Down-regulation of Rab27a in HL-60 cells by RNA interference did not affect JFC1/Slp1 expression but significantly decreased the secretion of MPO. Neither Rab27a nor JFC1/Slp1 was integrated into the phagolysosome membrane during phagocytosis. Neutrophils from Rab27a-deficient mice efficiently phagocytose zymosan opsonized particles and deliver MPO to the phagosome. We conclude that Rab27a and JFC1/Slp1 permit MPO release into the surrounding milieu and constitute key components of the secretory machinery of azurophilic granules in granulocytes. Our results suggest that the granules implicated in cargo release towards the surrounding milieu are molecularly and mechanistically different from those involved in their release towards the phagolysosome.
AU  - Munafó,DB
AU  - Johnson,JL
AU  - Ellis,BA
AU  - Rutschmann,S
AU  - Beutler,B
AU  - Catz,SD
DO  - 10.1042/BJ20060950
EP  - 239
PY  - 2007///
SP  - 229
TI  - Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes.
T2  - Biochem J
UR  - http://dx.doi.org/10.1042/BJ20060950
UR  - https://www.ncbi.nlm.nih.gov/pubmed/17090228
VL  - 402
ER  -
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