Advanced

The tetraspanin CD63 is involved in granule targeting of neutrophil elastase.

Källquist, Linda LU ; Hansson, Markus LU ; Persson, Ann-Maj LU ; Janssen, Hans; Calafat, Jero; Tapper, Hans LU and Olsson, Inge LU (2008) In Blood 112. p.3444-3454
Abstract
Targeting mechanisms of neutrophil elastase (NE) and other luminal proteins stored in myeloperoxidase (MPO)-positive secretory lysosomes/primary granules of neutrophils are unknown. These granules contain an integral membrane protein, CD63 with an adaptor protein-3-dependent granule delivery system. Therefore, we hypothesized that CD63 cooperates in granule delivery of the precursor of NE (proNE). Supporting this hypothesis, an association was demonstrated between CD63 and proNE upon coexpression in COS cells. This also involved augmented cellular retention of proNE requiring intact large extracellular loop of CD63. Furthermore, depletion of CD63 in promyelocytic HL-60 cells with RNA interference or a CD63 mutant caused reduction of... (More)
Targeting mechanisms of neutrophil elastase (NE) and other luminal proteins stored in myeloperoxidase (MPO)-positive secretory lysosomes/primary granules of neutrophils are unknown. These granules contain an integral membrane protein, CD63 with an adaptor protein-3-dependent granule delivery system. Therefore, we hypothesized that CD63 cooperates in granule delivery of the precursor of NE (proNE). Supporting this hypothesis, an association was demonstrated between CD63 and proNE upon coexpression in COS cells. This also involved augmented cellular retention of proNE requiring intact large extracellular loop of CD63. Furthermore, depletion of CD63 in promyelocytic HL-60 cells with RNA interference or a CD63 mutant caused reduction of cellular NE. However, the proNE steady state level was similar to wild type in CD63-depleted clones making it feasible to examine possible effects of CD63 on NE trafficking. Thus, depletion of CD63 led to reduced processing of proNE into mature NE and reduced constitutive secretion. Furthermore, CD63 -depleted cells showed a lack of morphologically normal granules, but contained MPO-positive cytoplasmic vacuoles with a lack of proNE and NE. Collectively, our data suggest that granule proteins may cooperate in targeting; CD63 can be involved in ER or Golgi export, cellular retention and granule targeting of proNE before storage as mature NE. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
112
pages
3444 - 3454
publisher
American Society of Hematology
external identifiers
  • wos:000259866100061
  • pmid:18669870
  • scopus:54049113079
ISSN
1528-0020
DOI
10.1182/blood-2007-10-116285
language
English
LU publication?
yes
id
d4d502cc-9b6f-4aae-853b-f4c4074cf45e (old id 1223625)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18669870?dopt=Abstract
date added to LUP
2008-09-11 13:30:37
date last changed
2017-09-03 04:51:04
@article{d4d502cc-9b6f-4aae-853b-f4c4074cf45e,
  abstract     = {Targeting mechanisms of neutrophil elastase (NE) and other luminal proteins stored in myeloperoxidase (MPO)-positive secretory lysosomes/primary granules of neutrophils are unknown. These granules contain an integral membrane protein, CD63 with an adaptor protein-3-dependent granule delivery system. Therefore, we hypothesized that CD63 cooperates in granule delivery of the precursor of NE (proNE). Supporting this hypothesis, an association was demonstrated between CD63 and proNE upon coexpression in COS cells. This also involved augmented cellular retention of proNE requiring intact large extracellular loop of CD63. Furthermore, depletion of CD63 in promyelocytic HL-60 cells with RNA interference or a CD63 mutant caused reduction of cellular NE. However, the proNE steady state level was similar to wild type in CD63-depleted clones making it feasible to examine possible effects of CD63 on NE trafficking. Thus, depletion of CD63 led to reduced processing of proNE into mature NE and reduced constitutive secretion. Furthermore, CD63 -depleted cells showed a lack of morphologically normal granules, but contained MPO-positive cytoplasmic vacuoles with a lack of proNE and NE. Collectively, our data suggest that granule proteins may cooperate in targeting; CD63 can be involved in ER or Golgi export, cellular retention and granule targeting of proNE before storage as mature NE.},
  author       = {Källquist, Linda and Hansson, Markus and Persson, Ann-Maj and Janssen, Hans and Calafat, Jero and Tapper, Hans and Olsson, Inge},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {3444--3454},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {The tetraspanin CD63 is involved in granule targeting of neutrophil elastase.},
  url          = {http://dx.doi.org/10.1182/blood-2007-10-116285},
  volume       = {112},
  year         = {2008},
}