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Verboon, J.M., Rincon-Arano, H., Werwie, T.R., Delrow, J.J., Scalzo, D., Nandakumar, V., Groudine, M., Parkhurst, S.M. (2015). Wash interacts with lamin and affects global nuclear organization.  Curr. Biol. 25(6): 804--810.
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Research paper

The cytoplasmic functions of Wiskott-Aldrich syndrome family (WAS) proteins are well established and include roles in cytoskeleton reorganization and membrane-cytoskeletal interactions important for membrane/vesicle trafficking, morphogenesis, immune response, and signal transduction. Misregulation of these proteins is associated with immune deficiency and metastasis 1-4. Cytoplasmic WAS proteins act as effectors of Rho family GTPases and polymerize branched actin through the Arp2/3 complex <up>1, 5</up>. Previously, we identified Drosophila washout (wash) as a new member of the WAS family with essential cytoplasmic roles in early development <up>6, 7</up>. Studies in mammalian cells and Dictyostelium suggest that WASH functions primarily in a multiprotein complex that regulates endosome shape and trafficking in an Arp2/3-dependent manner 8-11. However, roles for classically cytoplasmic proteins in the nucleus are beginning to emerge, in particular, as participants in the regulation of gene expression <up>12, 13</up>. Here, we show that Drosophila Wash is present in the nucleus, where it plays a key role in global nuclear organization. wash mutant and knockdown nuclei disrupt subnuclear structures/organelles and exhibit the abnormal wrinkled morphology reminiscent of those observed in diverse laminopathies 14-16. We find that nuclear Wash interacts with B-type Lamin (Lamin Dm0), and, like Lamin, Wash associates with constitutive heterochromatin. Wash knockdown increases chromatin accessibility of repressive compartments and results in a global redistribution of repressive histone modifications. Thus, our results reveal a novel role for Wash in modulating nucleus morphology and in the organization of both chromatin and non-chromatin nuclear sub-structures.

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Obtained with permission from Cell Press.
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PMC4366290 (PMC) (EuropePMC)
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