title: Molecular behavior adapts to context: heparanase functions as an extracellular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH.
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-beta-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.
authors.affiliation: Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Gilat
authors.forename: R
authors.initials: R
authors.lastname: Hershkoviz
authors.forename: I
authors.initials: I
authors.lastname: Goldkorn
authors.forename: L
authors.initials: L
authors.lastname: Cahalon
authors.forename: G
authors.initials: G
authors.lastname: Korner
authors.forename: I
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: O
authors.initials: O
authors.lastname: Lider
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000099175:Heparanase
chemical_list: D015815:Cell Adhesion Molecules; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D000099175:Heparanase