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PMID: 18413242 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis.

Methods in enzymology ·Vol. 438 ·2008-00-00 ·Pages 77-93

Kirchhausen T, Macia E, Pelish HE

Abstract

The large GTPase dynamin is essential for clathrin-dependent coated-vesicle formation. Dynasore is a cell-permeable small molecule that inhibits the GTPase activity of dynamin1, dynamin2 and Drp1, the mitochondrial dynamin. Dynasore was discovered in a screen of approximately 16,000 compounds for inhibitors of the dynamin2 GTPase. Dynasore is a noncompetitive inhibitor of dynamin GTPase activity and blocks dynamin-dependent endocytosis in cells, including neurons. It is fast acting (seconds) and its inhibitory effect in cells can be reversed by washout. Here we present a detailed synthesis protocol for dynasore, and describe a series of experiments used to analyze the inhibitory effects of dynasore on dynamin in vitro and to study the effects of dynasore on endocytosis in cells.

MeSH Terms
Animals Cytoskeleton/drug effects Dynamin II/antagonists & inhibitors Dynamins/analysis,antagonists & inhibitors Endocytosis Humans Hydrazones/pharmacology Protein Transport/drug effects Spodoptera
Chemicals
Hydrazones N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide Dynamin II Dynamins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kirchhausen Tom
Department of Cell Biology, Harvard Medical School, and IDI Immune Research Institute, Boston, Massachusetts, USA.
Macia Eric
Pelish Henry E
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Article Info
Journal
Methods in enzymology
Abbr.
Methods Enzymol
ISSN
0076-6879
DOI
10.1016/S0076-6879(07)38006-3
Published
2008-00-00
Pages
77-93
Language
English
Region
United States
NLM ID
0212271
PMCID
PMC2796620
Subset
IM
Grants
NIGMS NIH HHS · R01 GM036548 · United States
NIGMS NIH HHS · P01 GM062566 · United States
NIGMS NIH HHS · GM075252 · United States
NIGMS NIH HHS · R01 GM075252-04 · United States
NIGMS NIH HHS · GM03548 · United States
NIGMS NIH HHS · R01 GM075252 · United States
NIGMS NIH HHS · GM62566 · United States
External Links
PubMed source DOI: 10.1016/S0076-6879(07)38006-3 PMC Full Text View journal details
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