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The p53 cofactor JMY has been identified as a novel actin nucleation factor that promotes cell motility.
Endogenous JMY (green) in a ruffling B16F10 melanoma cell. Actin is shown in red and DNA in blue. Note the colocalization of JMY with actin at the leading edge (yellow). Image courtesy of J.B. Zuchero, University of California, San Francisco, USA.
Actin nucleation — the initial step in the formation of new actin filaments — can be induced by the actin-related protein 2/3 (Arp2/3) complex, which creates branched actin filaments, and spire, which creates unbranched filaments. A study now identifies the p53 cofactor JMY as a novel actin nucleation factor that combines the nucleating activities of these proteins to promote cell motility.
The authors observed a potential Arp2/3-activating sequence, WWWCA, in JMY. WWWCA contains three repeats of the actin monomer-binding domain WH2, in addition to a domain that can bind actin and Arp2/3. Intriguingly, in vitro, JMY can both activate Arp2/3 and, in the absence of Arp2/3, induce rapid actin polymerization. JMY produces branched filaments in the presence of Arp2/3, which is consistent with Arp2/3-mediated nucleation, but it also nucleates unbranched filaments in the absence of Arp2/3, which is consistent with spire-induced nucleation. Thus, JMY seems to combine the nucleating activities of Arp2/3 and spire.
Although JMY is predominantly nuclear in many cells, the authors observed JMY at the leading edge — the area closest to the direction of movement — in motile cells. This suggests a role for JMY in cell motility. Indeed, cells that overexpress JMY migrate faster in a wound healing assay that assesses cell motility. By contrast, knockdown of JMY decreases the rate of wound healing as a result of reduced actin nucleation. Significantly, JMY was specifically induced to the cell leading edge in response to wounding. Thus, the activity of JMY as a transcriptional cofactor and actin nucleation factor seems to be regulated by its cellular localization.
In short, the authors propose that JMY contributes to the assembly of the actin cytoskeleton and cell motility by first nucleating new filaments, using a spire-like mechanism, and then activating Arp2/3 to branch off these filaments.
ORIGINAL RESEARCH PAPER
- Zuchero , J. B. et al. p53-cofactor JMY is a multifunctional actin nucleation factor. Nature Cell Biol. 15 Mar 2009 (doi:10.1038/ncb1852)
FURTHER READING
- Goley , E. D. & Welch , M.D. The ARP2/3 complex: an actin nucleator comes of age. Nature Rev. Mol. Cell Biol. 7, 713–726 (2006) | Article |