Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease

Nat Commun. 2017 Apr 3;8:14816. doi: 10.1038/ncomms14816.


Human actin-related protein 2/3 complex (Arp2/3), required for actin filament branching, has two ARPC1 component isoforms, with ARPC1B prominently expressed in blood cells. Here we show in a child with microthrombocytopenia, eosinophilia and inflammatory disease, a homozygous frameshift mutation in ARPC1B (p.Val91Trpfs*30). Platelet lysates reveal no ARPC1B protein and greatly reduced Arp2/3 complex. Missense ARPC1B mutations are identified in an unrelated patient with similar symptoms and ARPC1B deficiency. ARPC1B-deficient platelets are microthrombocytes similar to those seen in Wiskott-Aldrich syndrome that show aberrant spreading consistent with loss of Arp2/3 function. Knockout of ARPC1B in megakaryocytic cells results in decreased proplatelet formation, and as observed in platelets from patients, increased ARPC1A expression. Thus loss of ARPC1B produces a unique set of platelet abnormalities, and is associated with haematopoietic/immune symptoms affecting cell lineages where this isoform predominates. In agreement with recent experimental studies, our findings suggest that ARPC1 isoforms are not functionally interchangeable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / deficiency*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism
  • Blood Platelet Disorders / metabolism*
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Blood Platelets / ultrastructure
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Shape
  • Disease Susceptibility
  • Fibrinogen / pharmacology
  • Gene Knockout Techniques
  • Humans
  • Inflammation / pathology*
  • Megakaryocytes / drug effects
  • Megakaryocytes / metabolism
  • Megakaryocytes / pathology
  • Mutation / genetics
  • Vasculitis / pathology
  • Wiskott-Aldrich Syndrome / pathology


  • ARPC1B protein, human
  • Actin-Related Protein 2-3 Complex
  • Actins
  • Fibrinogen