Wash interacts with lamin and affects global nuclear organization

Curr Biol. 2015 Mar 16;25(6):804-810. doi: 10.1016/j.cub.2015.01.052. Epub 2015 Mar 5.


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 [1, 5]. Previously, we identified Drosophila washout (wash) as a new member of the WAS family with essential cytoplasmic roles in early development [6, 7]. 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 [12, 13]. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / ultrastructure
  • Female
  • Gene Knockdown Techniques
  • Genes, Insect
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Lamins / genetics
  • Lamins / metabolism*
  • Male
  • Mutation
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Drosophila Proteins
  • Heterochromatin
  • Lam protein, Drosophila
  • Lamins
  • Vesicular Transport Proteins
  • WASH protein, Drosophila

Associated data

  • GEO/GSE59854