Megakaryocyte-specific Profilin1-deficiency alters microtubule stability and causes a Wiskott–Aldrich syndrome-like platelet defect

Markus Bender, Simon Stritt, Paquita Nurden, Judith M. M. van Eeuwijk, Barbara Zieger, Karim Kentouche, Harald Schulze, Henner Morbach, David Stegner, Katrin G. Heinze, Sebastian Dütting, Shuchi Gupta, Walter Witke, Hervé Falet, Alain Fischer, John H. Hartwig and Bernhard Nieswandt ()
Additional contact information
Markus Bender: University Hospital, University of Würzburg, Würzburg 97080
Simon Stritt: University Hospital, University of Würzburg, Würzburg 97080
Paquita Nurden: University Hospital, University of Würzburg, Würzburg 97080
Judith M. M. van Eeuwijk: University Hospital, University of Würzburg, Würzburg 97080
Barbara Zieger: University Medical Centre Freiburg, Freiburg 79106
Karim Kentouche: Jena University Hospital, Jena 07743
Harald Schulze: University Hospital, University of Würzburg, Würzburg 97080
Henner Morbach: University Hospital Würzburg
David Stegner: University Hospital, University of Würzburg, Würzburg 97080
Katrin G. Heinze: Rudolf Virchow Centre, University of Würzburg, Würzburg 97080, Germany
Sebastian Dütting: University Hospital, University of Würzburg, Würzburg 97080
Shuchi Gupta: University Hospital, University of Würzburg, Würzburg 97080
Walter Witke: Institute of Genetics, University of Bonn, Bonn 53115
Hervé Falet: Brigham and Women’s Hospital, Harvard Medical School
Alain Fischer: Unité d'Immunologie et d'Hématologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades
John H. Hartwig: Brigham and Women’s Hospital, Harvard Medical School
Bernhard Nieswandt: University Hospital, University of Würzburg, Würzburg 97080

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Wiskott–Aldrich syndrome (WAS) is caused by mutations in the WAS gene and is characterized by immunodeficiency, eczema and microthrombocytopenia. The molecular link between WAS mutations and microthrombocytopenia is unknown. Profilin1 (Pfn1) is a key actin-regulating protein that, besides actin, interacts with phosphoinositides and multiple proline-rich proteins, including the WAS protein (WASp)/WASp-interacting protein (WIP) complex. Here we report that mice with a megakaryocyte/platelet-specific Pfn1 deficiency display microthrombocytopenia due to accelerated turnover of platelets and premature platelet release into the bone marrow. Both Pfn1-null mouse platelets and platelets isolated from WAS patients contained abnormally organized and hyperstable microtubules. These results reveal an unexpected function of Pfn1 as a regulator of microtubule organization and point to a previously unrecognized mechanism underlying the platelet formation defect in WAS patients.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms5746 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5746

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms5746

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().