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Gouvernement du Canada / Government of Canada

Recherche

Opposing roles of syndecan-1 and syndecan-2 in polyethylenimine-mediated gene delivery

Par Conseil national de recherches du Canada

DOITrouver le DOI : https://doi.org/10.1074/jbc.M705424200
AuteurRechercher : 1; Rechercher : 1; Rechercher : 1
Affiliation
  1. Conseil national de recherches du Canada. Institut de recherche en biotechnologie du CNRC
FormatTexte, Article
Sujetbiotechnology; cells; endocytosis; gene expression; incomplet; proteoglycans; tail; transfection; polyethyleneimine; clustering
Résumé
Polyethylenimines (PEIs) are efficient non-viral vectors for gene transfer. Heparan sulphate proteoglycans have been proposed to be the cell surface receptors for PEI-DNA complexes (polyplexes). Here, we investigated if syndecan-1 (SDC1) and syndecan-2 (SDC2) may be involved in PEI-mediated transfection. Following addition of polyplexes to HEK293 cells, GFP-tagged SDCs rapidly formed clusters with PEI that were dependent of lipid rafts integrity. However, while SDC1 overexpression slightly enhanced PEImediated gene expression, SDC2 dramatically inhibited it. Confocal microscopy analysis showed that SDC1:polyplex endocytosis occurs within minutes after addition of polyplexes while that of SDC2:polyplexes takes hours. Expression of SDC1 cytoplasmic deletion mutants revealed that the SDC1 cytoplasmic tail is required for gene expression, but not for clustering or endocytosis, while overexpression of SDC1/SDC2 chimeras showed that SDC2 ectodomain is responsible for the inhibitory effect on gene transfer. Taken together, this study provides evidence that SDCs may have opposing effects on PEI-mediated transfection.
Date de publication
Maison d’éditionAmerican Society for Biochemistry and Molecular Biology
Dans
  • The Journal of Biological Chemistry 283, nº 12 : 7697–7704.
NoteDA - 20080124IS - 0021-9258 (Print)LA - ENGPT - JOURNAL ARTICLE
Langueanglais
Publications évaluées par des pairsOui
Numéro du CNRCNRCC 47810
NRC-BRI-47810
Numéro NPARC8925865
Exporter la noticeExporter en format RIS
Signaler une correctionSignaler une correction (s'ouvre dans un nouvel onglet)
Identificateur de l’enregistrementd3e4fdc5-a460-4644-b40c-5de321a324a3
Enregistrement créé2009-04-23
Enregistrement modifié2020-04-15
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