Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin
| Autor: | F. Pontillon, R. R. Majewski, Gabriel L. Navar, P. J. Verroust, J. H. Kaysen, F. O. Goda, Timothy G. Hammond |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Kidney Cortex Physiology Endosome Heymann Nephritis Antigenic Complex Endosomes Vacuole Biology urologic and male genital diseases Membrane Fusion Rats Sprague-Dawley medicine Animals Receptor Fluorescent Dyes Antibacterial agent Kidney Membrane Glycoproteins Rhodamines Aminoglycoside Flow Cytometry Fluoresceins In vitro Rats Cell biology Kidney Tubules medicine.anatomical_structure Biochemistry Mechanism of action Ethylmaleimide Fluorescein Gentamicins medicine.symptom Peptides |
| Zdroj: | American Journal of Physiology-Renal Physiology. 272:F117-F123 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.1997.272.1.f117 |
| Popis: | Megalin, a giant glycoprotein receptor heavily concentrated in the early endosomal pathway of renal proximal tubular cells, binds gentamicin with high affinity and delivers the drug to lysosomes. Utilizing an in vitro reconstitution assay we tested whether gentamicin-induced vacuolation is associated with inhibition of early endosomal fusion, as well as whether megalin plays a role in mediating these effects. Pretreatment of rats with gentamicin inhibited rat renal proximal tubular homotypic endosomal fusion. Administered simultaneously, gentamicin and polymers of polyaspartic acid, which protect against the hemodynamic effects of gentamicin nephrotoxicity, had no net effect on fusion. Polyaspartic acid alone had no effect on fusion. Antisera to the tail of the megalin/gentamicin receptor inhibited fusion, whereas non-specific controls had no effect. Peptides matching homologous NPXY repeat sequence motifs in the cytosolic tail stimulated endosomal fusion, whereas reverse sequence control peptides had no effect. These data suggest that gentamicin inhibition of endosomal fusion in the renal proximal tubule is a damage mechanism mediated by specific peptide sequences in the cytosolic tail of the giant gentamicin-binding receptor megalin and that receptors can effect the fusion properties of membranes in which they reside. |
| Databáze: | OpenAIRE |
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