The amyloid precursor protein(APP)of Alzheimer's disease and its paralog APLP2 modulate the Cu/Zn-NO-catalyzed degradation of glypican-1 heparan sulfate In vivo.
Cappai, Roberto ; Cheng, Fang LU ; Ciccotosto, Giuseppe D ; Needham, B Elise ; Masters, Colin L ; Multhaup, Gerd ; Fransson, Lars-Åke LU and Mani, Katrin LU
(2005)
In Journal of Biological Chemistry
280(14).
p.13913-13920
- Abstract
- Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma... (More)
- Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/134019
- author
- Cappai, Roberto
; Cheng, Fang
LU
; Ciccotosto, Giuseppe D
; Needham, B Elise
; Masters, Colin L
; Multhaup, Gerd
; Fransson, Lars-Åke
LU
and Mani, Katrin
LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 280
- issue
- 14
- pages
- 13913 - 13920
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000228095500092
- scopus:17144378275
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M409179200
- language
- English
- LU publication?
- yes
- id
- f65265b5-8657-4010-9dbc-6ef24bee0932 (old id 134019)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15677459&dopt=Abstract
- date added to LUP
- 2016-04-01 12:27:18
- date last changed
- 2023-09-02 08:16:30
@article{f65265b5-8657-4010-9dbc-6ef24bee0932,
abstract = {{Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1.}},
author = {{Cappai, Roberto and Cheng, Fang and Ciccotosto, Giuseppe D and Needham, B Elise and Masters, Colin L and Multhaup, Gerd and Fransson, Lars-Åke and Mani, Katrin}},
issn = {{1083-351X}},
language = {{eng}},
number = {{14}},
pages = {{13913--13920}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{The amyloid precursor protein(APP)of Alzheimer's disease and its paralog APLP2 modulate the Cu/Zn-NO-catalyzed degradation of glypican-1 heparan sulfate In vivo.}},
url = {{http://dx.doi.org/10.1074/jbc.M409179200}},
doi = {{10.1074/jbc.M409179200}},
volume = {{280}},
year = {{2005}},
}