Details

Autor(en) / Beteiligte

• Kahr, Walter H A
• Pluthero, Fred G
• Elkadri, Abdul
• Warner, Neil
• Drobac, Marko
• Chen, Chang Hua
• Lo, Richard W
• Li, Ling
• Li, Ren
• Li, Qi
• Thoeni, Cornelia
• Pan, Jie
• Leung, Gabriella
• Lara-Corrales, Irene
• Murchie, Ryan
• Cutz, Ernest
• Laxer, Ronald M
• Upton, Julia
• Roifman, Chaim M
• Yeung, Rae S M
• Brumell, John H
• Muise, Aleixo M

Titel

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

Ist Teil von

• Nature communications, 2017-04, Vol.8 (1), p.14816-14816, Article 14816

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.