TY - JOUR
T1 - Dynasore, a Cell-Permeable Inhibitor of Dynamin
AU - Macia, Eric
AU - Ehrlich, Marcelo
AU - Massol, Ramiro
AU - Boucrot, Emmanuel
AU - Brunner, Christian
AU - Kirchhausen, Tomas
N1 - Funding Information:
We thank W. Boll, S. Saffarian, M. Ma, and all the other members of our laboratory for their generous help and advice. We also thank the members of the Institute of Chemistry and Cell Biology, Harvard Medical School for help during the screening stage, and B. Fendly, R. Cerione, P. Chavrier, T. Dubois, A. Hall, O. Haller, G. Kochs, and J. Nunnari for kindly supplying cDNA constructs, protein, and the monoclonal antibody 13A9. We thank S.C. Harrison for inventing the term dynasore and suggesting its use. We acknowledge the generous support of the Perkin Fund to purchase part of the imaging equipment used here for live-cell imaging. M.E. was a Dorot Fellow with support from the Fulbright Foundation. E.B. is supported by a European Molecular Biology Organization long-term fellowship. This work was supported by National Institutes of Health GM62566-05, GM03548, and GM075252 (T.K).
PY - 2006/6
Y1 - 2006/6
N2 - Dynamin is essential for clathrin-dependent coated vesicle formation. It is required for membrane budding at a late stage during the transition from a fully formed pit to a pinched-off vesicle. Dynamin may also fulfill other roles during earlier stages of vesicle formation. We have screened about 16,000 small molecules and have identified 1, named here dynasore, that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases. Dynasore acts as a potent inhibitor of endocytic pathways known to depend on dynamin by rapidly blocking coated vesicle formation within seconds of dynasore addition. Two types of coated pit intermediates accumulate during dynasore treatment, ∪-shaped, half formed pits and O-shaped, fully formed pits, captured while pinching off. Thus, dynamin acts at two steps during clathrin coat formation; GTP hydrolysis is probably needed at both steps.
AB - Dynamin is essential for clathrin-dependent coated vesicle formation. It is required for membrane budding at a late stage during the transition from a fully formed pit to a pinched-off vesicle. Dynamin may also fulfill other roles during earlier stages of vesicle formation. We have screened about 16,000 small molecules and have identified 1, named here dynasore, that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases. Dynasore acts as a potent inhibitor of endocytic pathways known to depend on dynamin by rapidly blocking coated vesicle formation within seconds of dynasore addition. Two types of coated pit intermediates accumulate during dynasore treatment, ∪-shaped, half formed pits and O-shaped, fully formed pits, captured while pinching off. Thus, dynamin acts at two steps during clathrin coat formation; GTP hydrolysis is probably needed at both steps.
KW - CELLBIO
UR - http://www.scopus.com/inward/record.url?scp=33646892646&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2006.04.002
DO - 10.1016/j.devcel.2006.04.002
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C2 - 16740485
AN - SCOPUS:33646892646
SN - 1534-5807
VL - 10
SP - 839
EP - 850
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -