Ikarugamycin: A Natural Product Inhibitor of Clathrin‐Mediated Endocytosis. (8th August 2016)

• Record Type: Journal Article
• Authors: Elkin, Sarah R.; Oswald, Nathaniel W.; Reed, Dana K.; Mettlen, Marcel; MacMillan, John B.; Schmid, Sandra L.
• Is Part Of: Traffic. Volume 17:Number 10(2016)
• Page Start: 1139
• Page End: 1149
• Publication Date: 2016-08-08
• Subjects: caveolae‐mediated endocytosis -- clathrin‐independent endocytosis -- IC50 -- mammalian cells; Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12425
• Languages: English
• ISSNs: 1398-9219

Abstract

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. Abstract : The authors have characterized the natural product, ikarugamycin, to demonstrate its utility as a potent and selective acute inhibitor of clathrin‐mediated endocytosis.