Actin rapidly polymerizes into a filamentous (F) form in response to cell growth and motility triggers, such as serum stimulation. Serum stimulation also causes a transcription cofactor called MAL to promote transcription from target genes including actin. Reportedly, MAL can bind to monomeric (G) actin. It's possible then that serum-induced polymerization of actin, by lowering the cytoplasmic pool of G actin, frees up transcriptionally active MAL.
Live cell analyses by Vartiainen et al. now reveal that nuclear actin regulates MAL. Fluorescently labeled MAL shuttled back and forth to the nucleus in unstimulated cells, suggesting that G actin binding does not hold MAL in the cytoplasm, as might have been expected. Instead, G actin binding was necessary for rapidly exporting MAL from the nucleus.
Forcing MAL nuclear accumulation (by blocking an export protein) in unstimulated cells was not enough for MAL-regulated transcription, however. The authors therefore conclude that MAL must also dissociate from G actin to activate its target genes.
Through this feedback mechanism, actin is able to activate its own transcription (and that of actin regulators) when G actin supplies are running low. This ensures constant availability of the cytoskeletal building blocks. According to Treisman, there are several other MAL target genes whose functions in actin dynamics are anything but obvious. The team is now trying to determine how these apparent outsiders fit in to the scheme.