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

• DOI: 10.1038/ncomms14816
• Publication Date: 2017-04-03T09:32:38Z
• Authors: Walter H. A. Kahr; Fred G. Pluthero; Abdul Elkadri; Neil Warner; Marko Drobac; Chang Hua Chen; Richard W. Lo; Ling Li; Ren Li; Qi Li; Cornelia Thoeni; Jie Pan; Gabriella Leung; Irene Lara-Corrales; Ryan Murchie; Ernest Cutz; Ronald M. Laxer; Julia Upton; Chaim M. Roifman; Rae S. M. Yeung; John H Brumell; Aleixo M Muise
• Keywords: Component (thermodynamics)

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