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PMID: 18713753 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Forchlorfenuron alters mammalian septin assembly, organization, and dynamics.

The Journal of biological chemistry ·Vol. 283 ·No. 43 ·2008-10-24 ·Pages 29563-71

Hu Q, Nelson WJ, Spiliotis ET

Abstract

Septins are filamentous GTPases that associate with cell membranes and the cytoskeleton and play essential roles in cell division and cellular morphogenesis. Septins are implicated in many human diseases including cancer and neuropathies. Small molecules that reversibly perturb septin organization and function would be valuable tools for dissecting septin functions and could be used for therapeutic treatment of septin-related diseases. Forchlorfenuron (FCF) is a plant cytokinin previously shown to disrupt septin localization in budding yeast. However, it is unknown whether FCF directly targets septins and whether it affects septin organization and functions in mammalian cells. Here, we show that FCF alters septin assembly in vitro without affecting either actin or tubulin polymerization. In live mammalian cells, FCF dampens septin dynamics and induces the assembly of abnormally large septin structures. FCF has a low level of cytotoxicity, and these effects are reversed upon FCF washout. Significantly, FCF treatment induces mitotic and cell migration defects that phenocopy the effects of septin depletion by small interfering RNA. We conclude that FCF is a promising tool to study mammalian septin organization and functions.

MeSH Terms
Actins/chemistry Animals Cell Cycle Proteins/metabolism Cell Movement Collagen/chemistry Cytoskeletal Proteins Dogs GTP-Binding Proteins/metabolism HeLa Cells Humans Models, Biological Phenylurea Compounds/pharmacology Phosphoric Monoester Hydrolases/metabolism Protein Binding Pyridines/pharmacology Recombinant Proteins/chemistry Septins Wound Healing
Chemicals
Actins Cell Cycle Proteins Cytoskeletal Proteins Phenylurea Compounds Pyridines Recombinant Proteins Collagen Phosphoric Monoester Hydrolases GTP-Binding Proteins SEPTIN6 protein, human SEPTIN7 protein, human Septins N-(2-chloro-4-pyridyl)-N'-phenylurea
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hu Qicong
Department of Biology, Stanford University, Stanford, California 94305, USA.
Nelson W James
Spiliotis Elias T
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M804962200
Published
2008-10-24
Epub
2008-00-18
Pages
29563-71
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2570864
Subset
IM
Grants
NIGMS NIH HHS · GM35527 · United States
External Links
PubMed source DOI: 10.1074/jbc.M804962200 PMC Full Text View journal details
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