Probing the effect of an inhibitor of an ATPase domain of Hsc70 on clathrin-mediated endocytosis

Molecular BioSystems
Hyungseoph J ChoInjae Shin

Abstract

Hsc70 is known to be involved in clathrin-mediated endocytosis (CME) by which cells take up various extracellular materials. More specifically, this protein promotes the disassembly of clathrin-coated vesicles (CCVs) by directly binding to clathrin during CME. As the ATPase activity of Hsc70 is required for its association with clathrin, we have investigated the effect of an inhibitor (apoptozole, Az) of an ATPase domain of Hsc70 on CME. The results of biochemical studies show that Az binds to Hsc70 and Hsp70 without binding to other types of heat shock proteins. Structure-activity relationship studies provide information on the structural features responsible for the inhibition of the ATPase activity of Hsc70. The results obtained from cell experiments reveal that Az disrupts the interaction of Hsc70 with clathrin in cells, thereby leading to the accumulation of transferrin in CCVs and suppression of release of free Fe(3+) from CCVs during transferrin receptor-mediated endocytosis.

References

Jan 1, 1980·Annual Review of Biochemistry·P Aisen, I Listowsky
Mar 9, 2002·Science·F Ulrich Hartl, Manajit Hayer-Hartl
Nov 14, 2002·Pharmacological Reviews·Zhong Ming QianKwokping Ho
Mar 7, 2003·Nature·Sean D Conner, Sandra L Schmid
Oct 30, 2003·Chemistry & Biology·Calum A MacRae, Randall T Peterson
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Jason C YoungF Ulrich Hartl
Feb 3, 2005·Nature Reviews. Drug Discovery·Leonard I Zon, Randall T Peterson
Mar 17, 2005·Cellular and Molecular Life Sciences : CMLS·M P Mayer, B Bukau
May 10, 2007·Traffic·Evan Eisenberg, Lois E Greene
Jul 5, 2007·Nature Reviews. Molecular Cell Biology·Satyajit Mayor, Richard E Pagano
Jul 12, 2007·Journal of the American Chemical Society·Darren R WilliamsInjae Shin
Nov 6, 2007·Molecular Biology of the Cell·Iris RapoportTom Kirchhausen
Aug 30, 2008·Angewandte Chemie·Darren R WilliamsInjae Shin
Feb 18, 2010·Chemical Communications : Chem Comm·Min Hee LeeJong Seung Kim
Jul 23, 2011·Nature Reviews. Molecular Cell Biology·Harvey T McMahon, Emmanuel Boucrot
Mar 30, 2013·Cellular Logistics·Dipannita Dutta, Julie G Donaldson
Jul 22, 2014·Angewandte Chemie·Gun-Hee KimInjae Shin

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Citations

Oct 13, 2015·PloS One·Lindsay E EvansKeith Jones
Apr 20, 2017·Chembiochem : a European Journal of Chemical Biology·Ji Young HyunInjae Shin
Oct 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Akhouri Kishore RaghawanGhanshyam Swarup
Jun 16, 2017·Scientific Reports·Seong-Hyun ParkInjae Shin

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