JMY: Actin up in Cell Motility Migrate Faster in a Wound Healing Assay That Assesses Cell Motility

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Nature Reviews Molecular Cell Biology | aoP, published online 2 april 2009; doi:10.1038/nrm2678

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