Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY
Zuchero, J. Bradley
Belin, Brittany J.
Mullins, R. Dyche
MetadataShow full item record
Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.
© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Showing items related by title, author, creator and subject.
Beaulieu, Valerie; Da Silva, Nicolas; Pastor-Soler, Nuria; Brown, Christopher R.; Smith, Peter J. S.; Brown, Dennis; Breton, Sylvie (American Society for Biochemistry and Molecular Biology, 2004-12-09)The role of the actin cytoskeleton in regulating membrane protein trafficking is complex and depends on the cell type and protein being examined. Using the epididymis as a model system in which luminal acidification is ...
Schober, Joseph M.; Cain, Jeanine M.; Komarova, Yulia A.; Borisy, Gary G. (2009-04)Remodeling of actin and microtubule cytoskeletons is thought to be coupled; however, the interplay between these two systems is not fully understood. We show a microtubule end-binding protein, EB1, is required for formation ...
Arp2/3 complex inhibition radically alters lamellipodial actin architecture, suspended cell shape, and the cell spreading process Henson, John H.; Yeterian, Mesrob; Weeks, Richard M.; Medrano, Angela E.; Brown, Briana L.; Geist, Heather L.; Pais, Mollyann D.; Oldenbourg, Rudolf; Shuster, Charles B. (American Society for Cell Biology, 2015-01-07)Recent studies have investigated the dendritic actin cytoskeleton of the cell edge's lamellipodial (LP) region by experimentally decreasing the activity of the actin filament nucleator and branch former, the Arp2/3 complex. ...