Forchlorfenuron, a phenylurea cytokinin, disturbs septin organization in Saccharomyces cerevisiae

Abstract

Septins, which are involved in cytokinesis, have been identified in a variety of fungi and animal cells. For analysis of the function of septin, drugs targeting septin would be useful; however, no such drugs have been available hitherto. By serendipity, we found that forchlorfenuron (FCF, N-(2-chloro-4-pyridyl)-N-phenylurea, 4PU300), a synthetic plant cytokinin, disturbed cytokinesis in Saccharomyces cerevisiae . Upon administration of FCF, septin structures at the bud neck became deformed and filament-like septin appeared outside of the neck. Under these conditions, the localization of actin was normal and Gin4, which is localized at the bud neck in a septin-dependent manner, was found to remain at the location of apparently normal septin at the bud neck, whereas it was not co-localized to the deformed septin at the bud neck or to septin seen outside the bud neck. FCF administration immediately induced production of sporadic septin structures outside the bud neck, and these structures disappeared promptly upon removal of the drug. Taken together, these findings indicate that FCF maybe a promising drug for investigating the structure and function of septin.

Recruitment of septin cytoskeletal proteins by Botulinum toxin A protease determines its remarkable stability

“…This compound has been recently found to affect septin assembly, organization and dynamics, both in yeast and mammalian cells Iwase et al, 2004). FCF impaired normal septin assembly and induced the formation of abnormally large septin structures (DeMay et al, 2010;Hu et al, 2008).…”

Here come the septins: novel polymers that coordinate intracellular functions and organization

“…The development of chemical inhibitors that specifically interfere with septin assembly might overcome some of these limitations. For example, forchlorfenuron, a synthetic plant cytokinin, was recently found to disrupt yeast septin organization in a specific and reversible manner; however, this drug has yet to be tested in mammalian cells (Iwase et al, 2004). In future studies, the challenge is to understand how septins coordinate intracellular organization through an intricate network of hetero-oligomers and hetero-polymers.…”

Septin2 is modified by SUMOylation and required for chromosome congression in mouse oocytes

“…To determine whether septins are required for meiotic maturation, oocytes were matured in the presence or absence of Forchlorfenuron (FCF). FCF is a plant cytokinin previously shown to disrupt septin localization and cause cytokinesis defects in budding yeast; 39 it specifically affects disruption result in cytokinesis defects and accumulation of bi-nucleated cells, 32 we tested whether FCF had similar effects downstream of chromosome alignment in mouse oocytes. After 8 h of culture in M2 medium, when the majority of oocytes had reached the M I stage, we released the oocytes into medium containing FCF or DMSO (control) for an additional 4 h-culture.…”