Journal article
Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro
Nature chemical biology, Vol.2(1), pp.39-46
01/2006
DOI: 10.1038/nchembio751
PMID: 16408091
Abstract
Inspired by the usefulness of small molecules to study membrane traffic, we used high-throughput synthesis and phenotypic screening to discover secramine, a molecule that inhibits membrane traffic out of the Golgi apparatus by an unknown mechanism. We report here that secramine inhibits activation of the Rho GTPase Cdc42, a protein involved in membrane traffic, by a mechanism dependent upon the guanine dissociation inhibitor RhoGDI. RhoGDI binds Cdc42 and antagonizes its membrane association, nucleotide exchange and effector binding. In vitro, secramine inhibits Cdc42 binding to membranes, GTP and effectors in a RhoGDI-dependent manner. In cells, secramine mimics the effects of dominant-negative Cdc42 expression on protein export from the Golgi and on Golgi polarization in migrating cells. RhoGDI-dependent Cdc42 inhibition by secramine illustrates a new way to inhibit Rho GTPases with small molecules and provides a new means to study Cdc42, RhoGDI and the cellular processes they mediate.
Details
- Title: Subtitle
- Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro
- Creators
- Ji-Long Chen - University of IowaEnrique Rodriguez-Boulan - Cornell UniversityYan Feng - Functional Genomics, 5B-274, Novartis Institutes for BioMedical Research, Cambridge, USAMatthew D Shair - Harvard Stem Cell InstituteEric Macia - Department of Cell Biology and the CBR Institute for Biomedical Research, Harvard Medical School, Boston, USASusana B Salvarezza - Cornell UniversityHenry E Pelish - Department of Cell Biology and the CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.Tomas Kirchhausen - Harvard Stem Cell InstituteJeffrey R Peterson - Fox Chase Cancer CenterMark Stamnes - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature chemical biology, Vol.2(1), pp.39-46
- DOI
- 10.1038/nchembio751
- PMID
- 16408091
- NLM abbreviation
- Nat Chem Biol
- ISSN
- 1552-4450
- eISSN
- 1552-4469
- Language
- English
- Date published
- 01/2006
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297599302771
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