Molecular behavior adapts to context: Heparanase functions as an extraceuular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH

Dalia Gilat, Rami Hershkoviz, Isabela Goldkorn, Liora Cahalon, Gil Korner, Israel Vlodavsky, Ofer Lider

Research output: Contribution to journalArticlepeer-review

Abstract

Migration of lymphocytes into inflammatory sites requires their adhesion to the vascular endothelium and subendothelial extracellular matrix (ECM). The ensuing penetration of the ECM is associated with the expression of ECM-degrading enzymes, such as endo-β-D glucuronidase (heparanase), which cleaves heparan sulfate (HS) proteoglycans. We now report that, depending on the local pH, a mammalian heparanase can function either as an enzyme or as an adhesion molecule. At relatively acidified pH conditions, heparanase performs as an enzyme, degrading HS. In contrast, at the hydrogen ion concentration of a quiescent tissue, heparanase binds specifically to HS molecules without degrading them, and thereby anchors CD4+ human T lymphocytes. Thus, the local state of a tissue can regulate the activities of heparanase and can determine whether the molecule will function as an enzyme or as a proadhesive molecule.

Original languageEnglish
Pages (from-to)1929-1934
Number of pages6
JournalJournal of Experimental Medicine
Volume181
Issue number5
DOIs
StatePublished - 1 May 1995
Externally publishedYes

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