Ikarugamycin

A Natural Product Inhibitor of Clathrin-Mediated Endocytosis

Sarah R. Elkin, Nathaniel W. Oswald, Dana K. Reed, Marcel Mettlen, John B. MacMillan, Sandra L. Schmid

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low-density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 μm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking.

Original languageEnglish (US)
Pages (from-to)1139-1149
Number of pages11
JournalTraffic
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Clathrin
Endocytosis
Biological Products
Cell Line
Biochemistry
Macrophages
Plant Cells
ikarugamycin
Inhibitory Concentration 50
Microscopy
Microscopic examination
Cells
Anti-Bacterial Agents

Keywords

  • caveolae-mediated endocytosis
  • clathrin-independent endocytosis
  • IC
  • mammalian cells

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Ikarugamycin : A Natural Product Inhibitor of Clathrin-Mediated Endocytosis. / Elkin, Sarah R.; Oswald, Nathaniel W.; Reed, Dana K.; Mettlen, Marcel; MacMillan, John B.; Schmid, Sandra L.

In: Traffic, Vol. 17, No. 10, 01.10.2016, p. 1139-1149.

Research output: Contribution to journalArticle

Elkin, Sarah R. ; Oswald, Nathaniel W. ; Reed, Dana K. ; Mettlen, Marcel ; MacMillan, John B. ; Schmid, Sandra L. / Ikarugamycin : A Natural Product Inhibitor of Clathrin-Mediated Endocytosis. In: Traffic. 2016 ; Vol. 17, No. 10. pp. 1139-1149.
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