Megakaryocyte-specific Profilin1-deficiency alters microtubule stability and causes a Wiskott-Aldrich syndrome-like platelet defect. Nat Commun 2014 Sep 04;5:4746
Date
09/05/2014Pubmed ID
25187265DOI
10.1038/ncomms5746Scopus ID
2-s2.0-84920935863 (requires institutional sign-in at Scopus site) 81 CitationsAbstract
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.
Author List
Bender M, Stritt S, Nurden P, van Eeuwijk JM, Zieger B, Kentouche K, Schulze H, Morbach H, Stegner D, Heinze KG, Dütting S, Gupta S, Witke W, Falet H, Fischer A, Hartwig JH, Nieswandt BAuthor
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAnimals
Blood Platelets
Bone Marrow
Child
Child, Preschool
Cytoskeletal Proteins
Gene Expression Regulation
Hematopoiesis
Humans
Infant
Intracellular Signaling Peptides and Proteins
Male
Megakaryocytes
Mice
Microtubules
Mutation
Profilins
Signal Transduction
Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome Protein
