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Disruption of endocytosis through chemical inhibition of clathrin heavy chain function

Wim Dejonghe (UGent) , Isha Sharma (UGent) , Bram Denoo (UGent) , Steven De Munck (UGent) , Qing Lu (UGent) , Kiril Mishev (UGent) , Haydar Bulut, Evelien Mylle (UGent) , Riet De Rycke (UGent) , Mina Vasileva, et al.
(2019) NATURE CHEMICAL BIOLOGY. 15(6). p.641-649
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Abstract
Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.
Keywords
ENDOMEMBRANE TRAFFICKING, MEDIATED ENDOCYTOSIS, SMALL MOLECULES, DYNASORE, SYSTEM, PYTHON, GOLGI

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Chicago
Dejonghe, Wim, Isha Sharma, Bram Denoo, Steven De Munck, Qing Lu, Kiril Mishev, Haydar Bulut, et al. 2019. “Disruption of Endocytosis Through Chemical Inhibition of Clathrin Heavy Chain Function.” Nature Chemical Biology 15 (6): 641–649.
APA
Dejonghe, Wim, Sharma, I., Denoo, B., De Munck, S., Lu, Q., Mishev, K., Bulut, H., et al. (2019). Disruption of endocytosis through chemical inhibition of clathrin heavy chain function. NATURE CHEMICAL BIOLOGY, 15(6), 641–649.
Vancouver
1.
Dejonghe W, Sharma I, Denoo B, De Munck S, Lu Q, Mishev K, et al. Disruption of endocytosis through chemical inhibition of clathrin heavy chain function. NATURE CHEMICAL BIOLOGY. 2019;15(6):641–9.
MLA
Dejonghe, Wim et al. “Disruption of Endocytosis Through Chemical Inhibition of Clathrin Heavy Chain Function.” NATURE CHEMICAL BIOLOGY 15.6 (2019): 641–649. Print.
@article{8617277,
  abstract     = {Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.},
  author       = {Dejonghe, Wim and Sharma, Isha and Denoo, Bram and De Munck, Steven and Lu, Qing and Mishev, Kiril and Bulut, Haydar and Mylle, Evelien and De Rycke, Riet and Vasileva, Mina and Savatin, Daniel and Nerinckx, Wim and Staes, An and Drozdzecki, Andrzej and Audenaert, Dominique and Yperman, Klaas and Madder, Annemieke and Friml, Jiří and Van Damme, Daniël and Gevaert, Kris and Haucke, Volker and Savvides, Savvas and Winne, Johan and Russinova, Eugenia},
  issn         = {1552-4450},
  journal      = {NATURE CHEMICAL BIOLOGY},
  keywords     = {ENDOMEMBRANE TRAFFICKING,MEDIATED ENDOCYTOSIS,SMALL MOLECULES,DYNASORE,SYSTEM,PYTHON,GOLGI},
  language     = {eng},
  number       = {6},
  pages        = {641--649},
  title        = {Disruption of endocytosis through chemical inhibition of clathrin heavy chain function},
  url          = {http://dx.doi.org/10.1038/s41589-019-0262-1},
  volume       = {15},
  year         = {2019},
}

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