ADF/n-cofilin-dependent actin turnover determines platelet formation and sizing.
The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin-mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.
Bender
Markus
M
Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
Eckly
Anita
A
Hartwig
John H
JH
Elvers
Margitta
M
Pleines
Irina
I
Gupta
Shuchi
S
Krohne
Georg
G
Jeanclos
Elisabeth
E
Gohla
Antje
A
Gurniak
Christine
C
Gachet
Christian
C
Witke
Walter
W
Nieswandt
Bernhard
B
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D048430:Cell Shape; D048429:Cell Size; D002470:Cell Survival; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D051345:Destrin / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010976:Platelet Count; D013163:Splenomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D000199:Actins; D051338:Cofilin 1; D051345:Destrin; C495825:Dstn protein, mouse; D005340:Fibrinogen; D013917:Thrombin