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A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4

Authors
  • Habeler, Matthias1
  • Lindner, Herbert H.1
  • Redl, Bernhard1
  • 1 Medical University Innsbruck, Innrain 80, A-6020 , (Austria)
Type
Published Article
Journal
Biological Chemistry
Publisher
Walter de Gruyter GmbH
Publication Date
Jul 16, 2020
Volume
401
Issue
9
Pages
1081–1092
Identifiers
DOI: 10.1515/hsz-2020-0132
Source
De Gruyter
Keywords
License
Green

Abstract

Lipocalins, small extracellular hydrophobic molecule carriers, can be internalized by a variety of different cells. However, to date receptors have only been identified for human lipocalins. Here, we specifically investigated uptake mechanisms for lipocalins ß-lactoglobulin and Fel d 4 in HeLa and Chinese hamster ovary (CHO) cells. We provide evidence that cell surface heparan sulphate proteoglycan is essential for internalization of these lipocalins. In HeLa cells, lipocalin uptake was inhibited by competition with soluble heparin, enzymatic digestion of cellular heparan sulphate by heparinase and inhibition of its biosynthesis by sodium chlorate. Biochemical studies by heparin affinity chromatography and colocalization studies further supported a role of heparan sulphate proteoglycan in lipocalin uptake. Finally, lipocalin uptake was blocked in CHO mutant cells defective in glycosaminoglycan biosynthesis whereas in wild-type cells it was clearly detectable. Thus, cell surface heparan sulphate proteoglycan represents a novel component absolutely participating in the cellular uptake of some lipocalins.

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