作者: Isabelle C Becker , Inga Scheller , Lou M Wackerbarth , Sarah Beck , Tobias Heib
DOI: 10.1182/BLOODADVANCES.2019001303
关键词:
摘要: Rearrangements of the microtubule (MT) and actin cytoskeleton are pivotal for platelet biogenesis. Hence, defects in actin- or MT-regulatory proteins associated with disorders humans mice. Previous studies mice revealed that loss actin-depolymerizing factor homology (ADF-H) protein Cofilin1 (Cof1) megakaryocytes (MKs) results a moderate macrothrombocytopenia but normal MK numbers, whereas deficiency another ADF-H protein, Twinfilin1 (Twf1), does not affect production function. However, recent yeast have indicated critical synergism between Twf1 Cof1 regulation dynamics. We therefore investigated biogenesis function lacking both lineage. In contrast to single either Twf1/Cof1 double (DKO) resulted severe dramatically increased numbers bone marrow spleen. DKO MKs exhibited defective proplatelet formation vitro vivo as well impaired spreading altered assembly podosome-like structures on collagen fibrinogen vitro. These were aberrant F-actin accumulation and, remarkably, hyperstable MT, which appears be caused by dysregulation MT-binding mDia1 adenomatous polyposis coli. Surprisingly, mild functional described Cof1-deficient platelets only slightly aggravated suggesting largely dispensable peripheral blood. summary, these findings reveal redundant functions ensuring balanced actin/microtubule crosstalk during thrombopoiesis possibly humans.