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Role of intracellular pH in ligand internalization

Journal Article · · J. Cell. Physiol.; (United States)

Internalization of EGF and transferrin measured as the rate of uptake of /sup 125/I-labeled ligands was compared in the cell line CCL39 and a mutant derivative, PS120, lacking the Na/sup +//H/sup +/ antiport system. No significant alteration was detected between the two cell lines. In contrast, pretreatment of the mutant cells PS-120 with 20 mM NH/sub 4/Cl for 30 min to decrease persistently intracellular pH resulted in an increase in /sup 125/I-EGF and /sup 125/I-transferrin uptake by 60% and 25%, respectively. However, similar NH/sub 4/Cl pretreatment of the parental cell line, CCL-39, which only affected intracellular pH very transiently did not cause an increase of ligand uptake. The binding of /sup 125/I-EGF to CCL-39 and PS-120 cells with or without NH/sub 4/Cl pretreatment showed that NH/sub 4/Cl pretreatment did not affect EGF binding in either CCL-39 or PS-120 cells. Since cells regulate intracellular pH by ion transport systems, we also examined the role of Na/sup +/, K/sup +/ -ATPase. Ouabain, an inhibitor of Na/sup +/, K/sup +/ -ATPases, showed no effect on /sup 125/I-EGF uptake in either of the cell types with or without NH/sub 4/Cl pretreatment. Taken together, these results suggest that the plasma membrane-bound Na/sup +//H/sup +/ antiport, a major pH/sub i/-regulating system in vertebrates, indirectly plays a role in ligand internalization through regulation of intracellular pH.

Research Organization:
National Institutes of Health, Bethesda, MD
OSTI ID:
6942636
Journal Information:
J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 128:1; ISSN JCLLA
Country of Publication:
United States
Language:
English