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Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin.

Publication ,  Journal Article
Hammond, TG; Majewski, RR; Kaysen, JH; Goda, FO; Navar, GL; Pontillon, F; Verroust, PJ
Published in: Am J Physiol
January 1997

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.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

January 1997

Volume

272

Issue

1 Pt 2

Start / End Page

F117 / F123

Location

United States

Related Subject Headings

  • Rhodamines
  • Rats, Sprague-Dawley
  • Rats
  • Peptides
  • Membrane Glycoproteins
  • Membrane Fusion
  • Male
  • Kidney Tubules
  • Kidney Cortex
  • Heymann Nephritis Antigenic Complex
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hammond, T. G., Majewski, R. R., Kaysen, J. H., Goda, F. O., Navar, G. L., Pontillon, F., & Verroust, P. J. (1997). Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin. Am J Physiol, 272(1 Pt 2), F117–F123. https://doi.org/10.1152/ajprenal.1997.272.1.F117
Hammond, T. G., R. R. Majewski, J. H. Kaysen, F. O. Goda, G. L. Navar, F. Pontillon, and P. J. Verroust. “Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin.Am J Physiol 272, no. 1 Pt 2 (January 1997): F117–23. https://doi.org/10.1152/ajprenal.1997.272.1.F117.
Hammond TG, Majewski RR, Kaysen JH, Goda FO, Navar GL, Pontillon F, et al. Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin. Am J Physiol. 1997 Jan;272(1 Pt 2):F117–23.
Hammond, T. G., et al. “Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin.Am J Physiol, vol. 272, no. 1 Pt 2, Jan. 1997, pp. F117–23. Pubmed, doi:10.1152/ajprenal.1997.272.1.F117.
Hammond TG, Majewski RR, Kaysen JH, Goda FO, Navar GL, Pontillon F, Verroust PJ. Gentamicin inhibits rat renal cortical homotypic endosomal fusion: role of megalin. Am J Physiol. 1997 Jan;272(1 Pt 2):F117–F123.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

January 1997

Volume

272

Issue

1 Pt 2

Start / End Page

F117 / F123

Location

United States

Related Subject Headings

  • Rhodamines
  • Rats, Sprague-Dawley
  • Rats
  • Peptides
  • Membrane Glycoproteins
  • Membrane Fusion
  • Male
  • Kidney Tubules
  • Kidney Cortex
  • Heymann Nephritis Antigenic Complex