Advanced

Sorting of Von Willebrand factor to lysosome-related granules of haematopoietic cells

Rosén, Hanna LU ; Calafat, Jero; Holmberg, Lars LU and Olsson, Inge LU (2004) In Biochemical and Biophysical Research Communications 315(3). p.671-678
Abstract
The aim of this work was to investigate sorting mechanisms of von Willebrand factor (VWF) when expressed in haematopoietic cells. The processing and sorting of both the wild-type VWF and a multimerization defective propeptide-mutant (VWFm) were investigated after expression in the 32D cell line. Normal proteolytic processing was observed for both proteins, however the processing of VWFm was much slower and a large portion was unprocessed. Results from subcellular fractionation and immunoelectron microscopy confirmed that a part of VWF, but not VWFm, was targeted to lysosome-related granules. Partial constitutive secretion was also observed for all forms of VWF and VWFm. Inhibition of acidification by chloroquine blocked VWF processing but... (More)
The aim of this work was to investigate sorting mechanisms of von Willebrand factor (VWF) when expressed in haematopoietic cells. The processing and sorting of both the wild-type VWF and a multimerization defective propeptide-mutant (VWFm) were investigated after expression in the 32D cell line. Normal proteolytic processing was observed for both proteins, however the processing of VWFm was much slower and a large portion was unprocessed. Results from subcellular fractionation and immunoelectron microscopy confirmed that a part of VWF, but not VWFm, was targeted to lysosome-related granules. Partial constitutive secretion was also observed for all forms of VWF and VWFm. Inhibition of acidification by chloroquine blocked VWF processing but allowed unprocessed pro-VWF targeting to dense organelles. In conclusion, our observations are consistent with VWF multimerization being of importance in cellular retention and targeting to lysosome-related organelles in haematopoietic cells, suggesting a role of protein aggregation for sorting in these cells. (C) 2004 Elsevier Inc. All rights reserved. (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
Biochemical and Biophysical Research Communications
volume
315
issue
3
pages
671 - 678
publisher
Elsevier
external identifiers
  • wos:000189291900022
  • scopus:1242340425
ISSN
1090-2104
DOI
10.1016/j.bbrc.2004.01.106
language
English
LU publication?
yes
id
53669d4f-9966-46a8-8d9d-bf895fe53675 (old id 120465)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14975753&dopt=Abstract
date added to LUP
2007-07-09 13:55:11
date last changed
2017-07-30 04:25:25
@article{53669d4f-9966-46a8-8d9d-bf895fe53675,
  abstract     = {The aim of this work was to investigate sorting mechanisms of von Willebrand factor (VWF) when expressed in haematopoietic cells. The processing and sorting of both the wild-type VWF and a multimerization defective propeptide-mutant (VWFm) were investigated after expression in the 32D cell line. Normal proteolytic processing was observed for both proteins, however the processing of VWFm was much slower and a large portion was unprocessed. Results from subcellular fractionation and immunoelectron microscopy confirmed that a part of VWF, but not VWFm, was targeted to lysosome-related granules. Partial constitutive secretion was also observed for all forms of VWF and VWFm. Inhibition of acidification by chloroquine blocked VWF processing but allowed unprocessed pro-VWF targeting to dense organelles. In conclusion, our observations are consistent with VWF multimerization being of importance in cellular retention and targeting to lysosome-related organelles in haematopoietic cells, suggesting a role of protein aggregation for sorting in these cells. (C) 2004 Elsevier Inc. All rights reserved.},
  author       = {Rosén, Hanna and Calafat, Jero and Holmberg, Lars and Olsson, Inge},
  issn         = {1090-2104},
  language     = {eng},
  number       = {3},
  pages        = {671--678},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Sorting of Von Willebrand factor to lysosome-related granules of haematopoietic cells},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2004.01.106},
  volume       = {315},
  year         = {2004},
}