Abstract:
:Like many physiological ligands, several viruses and toxins enter mammalian cells through receptor-mediated endocytosis. Once internalized, the nucleic acids of several viruses and the toxic subunit of diphtheria toxin gain access to the cytosol of the host cell through an acidic intracellular compartment. In this report, we present evidence that one class of mutants of Chinese hamster ovary (CHO)-K1 cells, which is "cross-resistant" to Pseudomonas exotoxin A, diphtheria toxin, and several animal viruses, has a defect in acidification of the endosome. Cells were allowed to internalize fluorescein isothiocyanate-conjugated dextran before subcellular fractionation. Fluorescence measurements on subcellular fractions permitted measurement of the internal pH of the isolated endosomes and lysosomes. Our results show that (i) endosomes and lysosomes from CHO-K1 cells maintain an acidic pH, (ii) acidification of both endosomes and lysosomes is mediated by a Mg2+/ATP-dependent process, (iii) GTP can satisfy the ATP requirement for acidification of lysosomes but not of endosomes, and (iv) at least one class of mutants that is cross-resistant to toxins and animal viruses has a defect in the ATP-dependent acidification of their endosomes. These studies provide biochemical and genetic evidence that the mechanisms of acidification of endosomes and lysosomes are distinct and that a defect in acidification of endosomes is one biochemical basis for cross-resistance to toxins and viruses.
journal_name
Proc Natl Acad Sci U S Aauthors
Merion M,Schlesinger P,Brooks RM,Moehring JM,Moehring TJ,Sly WSdoi
10.1073/pnas.80.17.5315subject
Has Abstractpub_date
1983-09-01 00:00:00pages
5315-9issue
17eissn
0027-8424issn
1091-6490journal_volume
80pub_type
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