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

[wiskott-aldrich syndrome]

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 . Profilin 1 (Pfn 1 ) 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 Pfn 1 deficiency display microthrombocytopenia due to accelerated turnover of platelets and premature platelet release into the bone marrow . Both Pfn 1 -null mouse platelets and platelets isolated from WAS patients contained abnormally organized and hyperstable microtubules . These results reveal an unexpected function of Pfn 1 as a regulator of microtubule organization and point to a previously unrecognized mechanism underlying the platelet formation defect in WAS patients .

Diseases
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Diseases presenting "is characterized by immunodeficiency" symptom

wiskott-aldrich syndrome

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