Non-specificity of Pitstop 2 in clathrin-mediated endocytosis

Biology Open

Anna K. Willox¹  Stephen J. Royle¹  Yasmina M. E. Sahraoui¹ 

[1] Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK;

关键词: Clathrin;    Endocytosis;    Pitstop;    Small-molecule inhibitor;   

DOI  :  10.1242/bio.20147955

来源: DOAJ

【 摘 要 】

Small molecule inhibitors of clathrin-mediated endocytosis are highly desired for the dissection of membrane trafficking pathways in the lab and for potential use as anti-infectives in the clinic. One inhibition strategy is to prevent clathrin from contacting adaptor proteins so that clathrin-mediated endocytosis cannot occur. “Pitstop” compounds have been developed that block only one of the four functional interaction sites on the N-terminal domain of clathrin heavy chain. Despite this limitation, Pitstop 2 causes profound inhibition of clathrin-mediated endocytosis. In this study, we probed for non-specific activity of Pitstop 2 by examining its action in cells expressing clathrin heavy chain harbouring mutations in the N-terminal domain interaction sites. We conclude that the inhibition observed with this compound is due to non-specificity, i.e. it causes inhibition away from its proposed mode of action. We recommend that these compounds be used with caution in cells and that they should not be used to conclude anything of the function of clathrin's N-terminal domain.

【 授权许可】

Unknown