Heparin interaction with cultured cells: possible role of fibronectin in uncoupling surface binding and endocytosis

Autor: Wei-Chiang Shen, Hugues J.-P. Ryser, Nader Morad
Rok vydání: 1983
Předmět:
Zdroj: Cell biology international reports. 7(11)
ISSN: 0309-1651
Popis: Cellular uptake of 3H-heparin by cultured Chinese hamster ovary cells does not follow the pattern that would be expected on the basis of binding kinetics. It is essentially non-saturable and its low pinocytotic index is consistent with fluid-phase endocytosis, while surface binding is saturable and suggests the presence of specific receptors. Most of the surface-bound heparin is released into the medium and only minimal amounts are internalized when temperature is shifted from 0 ° to 37 °C. This uncoupling of surface binding and endocytosis may be due to the binding of heparin to an external surface macromolecule that is only loosely attached to the plasma membrane, and may therefore escape endocytosis. Fibronectin is a likely candidate to provide that type of binding site. Heparin has been found to bind specifically to a number of mammalian cells (Kjellen et al., 1977; Glimelius et al., 1978;Shanberge et al., 1976; Fabian et al., 1978), but no attempt was made in those studies to distinguish between surface binding and cellular uptake. Heparin is transported into cells when complexed to other macromolecules (Fabian et al., 1978; Shen and Ryser, 1981;Morad et al., 1982) and does then exert some cellular effects (Shen and Ryser, 1981). Despite the wide clinical use of heparin, little is known about its membrane transport and intracellular effects, although endocytosis of other polyanions has been shown to inhibit phago-lysosomal fusion in macrophages (Geisow et al., 1980). We show here that endocytosis of heparin does occur in Chinese hamster ovary (CHO) cells, but that it follows a most unusual pattern in that it does not correlate with heparin binding to the cell surface. We suggest that this uncoupling is due to the binding of heparin to an external membrane macromolecule that, like fibronectin, is easily shed into the medium.
Databáze: OpenAIRE