Abstract
Many cellular structures are assembled from networks of actin filaments, and the architecture of these networks depends on the mechanism by which the filaments are formed. Several classes of proteins are known to assemble new filaments, including the Arp2/3 complex, which creates branched filament networks, and Spire, which creates unbranched filaments1,2. We find that JMY, a vertebrate protein first identified as a transcriptional co-activator of p53, combines these two nucleating activities by both activating Arp2/3 and assembling filaments directly using a Spire-like mechanism. Increased levels of JMY expression enhance motility, whereas loss of JMY slows cell migration. When slowly migrating HL-60 cells are differentiated into highly motile neutrophil-like cells, JMY moves from the nucleus to the cytoplasm and is concentrated at the leading edge. Thus, JMY represents a new class of multifunctional actin assembly factor whose activity is regulated, at least in part, by sequestration in the nucleus.
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Acknowledgements
We thank A. Kelly and R. Manlove for sequence analysis; O. Akin for help with Matlab scripts and advice; C. Campbell and H. Bourne for critical reading of the manuscript; and O. Weiner, S. Wilson, P. Temkin, E. Oh, C. Vizcarra, S. Cai, M. D'Ambrosio, K. Campellone, and members of the Mullins laboratory for reagents and helpful discussions. This work was supported by grants from the National Institutes of Health, the American Heart Association Predoctoral Fellowship (J.B.Z.), Medical Research Council funding (A.S.C.), and the Burroughs-Wellcome Fund Career Award in the Biomedical Sciences Fellowship (M.E.Q.).
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J.B.Z., A.S.C. and M.E.Q. conducted the experiments and analysed the results. J.B.Z., A.S.C., M.E.Q., N.B.T. and R.D.M. conceived the experiments and wrote the manuscript.
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Zuchero, J., Coutts, A., Quinlan, M. et al. p53-cofactor JMY is a multifunctional actin nucleation factor. Nat Cell Biol 11, 451–459 (2009). https://doi.org/10.1038/ncb1852
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DOI: https://doi.org/10.1038/ncb1852
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