Research ArticleCell Biology

Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration

See allHide authors and affiliations

Science Signaling  10 Nov 2015:
Vol. 8, Issue 402, pp. ra112
DOI: 10.1126/scisignal.aad2959

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

F-actin delivers MKL1 to the nucleus

The highly dynamic actin cytoskeleton maintains cell shape, enables cell movement, and contributes to cell division. Perhaps surprisingly, actin cytoskeletal dynamics also regulate gene expression. Persistent cell migration involves both cytoskeletal reorganization and expression of specific genes. The transcription factor serum response factor (SRF) and the coactivator megakaryoblastic leukemia 1 (MKL1) mediate transcriptional changes in response to external signals that affect actin dynamics. Globular actin (G-actin) keeps MKL1 in the cytosol, and signals that promote the formation of filamentous actin (F-actin) trigger the nuclear translocation of MKL1 and transcriptional activation of SRF. MKL1 not only had to dissociate from G-actin but also had to associate with the F-actin binding protein filamin A (FLNA) to promote SRF activity. Indeed, FLNA bound to the promoters of the same genes that are regulated by MKL1-SRF. Blocking the interaction between FLNA and MKL1—by inhibiting actin polymerization, mutating the FLNA interaction site on MKL1, or reducing the amount of FLNA—impaired the expression of MKL1-SRF target genes. Thus, actin dynamics not only actively move cells but also actively mediate the transcriptional activity of regulators needed for cellular movement.

View Full Text

Stay Connected to Science Signaling