Open Close
Reference
Citation
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.
FlyBase ID
FBrf0227864
Publication Type
Research paper
Abstract
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.
Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC4366290 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Curr. Biol.
    Title
    Current Biology
    Publication Year
    1991-
    ISBN/ISSN
    0960-9822
    Data From Reference
    Aberrations (3)
    Alleles (4)
    Genes (2)
    Physical Interactions (4)
    Cell Lines (2)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (2)
    Transgenic Constructs (2)