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Defective N-sulfati...
Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development
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Abramsson, Alexandra, 1973 (author)
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- Kurup, Sindhulakshmi (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Busse, Marta (author)
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- Yamada, Shuhei (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Lindblom, Per (author)
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- Schallmeiner, Edith (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Stenzel, Denise (author)
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Sauvaget, Dominique (author)
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- Ledin, Johan (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Ringvall, Maria (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Landegren, Ulf (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Kjellén, Lena (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Bondjers, Göran, 1944 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Li, Jin-Ping (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Lindahl, Ulf (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Spillmann, Dorothe (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Betsholtz, Christer, 1959 (author)
- Karolinska Institutet
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Gerhardt, Holger, 1969 (author)
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(creator_code:org_t)
- 2007-02-08
- 2007
- English.
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In: GENES & DEVELOPMENT. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 21:3, s. 316-331
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http://genesdev.cshl...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor β (PDGFRβ) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- smooth-muscle-cells
- growth-factor
- diabetic-retinopathy
- neonatal lethality
- mouse-brain
- a-chain
- mice
- identification
- deficient
- domain
- PDGF-B
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Abramsson, Alexa ...
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Kurup, Sindhulak ...
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Busse, Marta
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Yamada, Shuhei
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Lindblom, Per
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Schallmeiner, Ed ...
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show more...
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Stenzel, Denise
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Sauvaget, Domini ...
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Ledin, Johan
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Ringvall, Maria
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Landegren, Ulf
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Kjellén, Lena
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Bondjers, Göran, ...
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Li, Jin-Ping
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Lindahl, Ulf
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Spillmann, Dorot ...
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Betsholtz, Chris ...
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Gerhardt, Holger ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Developmental Bi ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
- Articles in the publication
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GENES & DEVELOPM ...
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet