Myosin IIA is critical for organelle distribution and F-actin organization in megakaryocytes and platelets.
During proplatelet formation, a relatively homogeneous content of organelles is transported from the megakaryocyte (MK) to the nascent platelets along microtubule tracks. We found that platelets from Myh9(-/-) mice and a MYH9-RD patient were heterogeneous in their organelle content (granules and mitochondria). In addition, Myh9(-/-) MKs have an abnormal cytoplasmic clustering of organelles, suggesting that the platelet defect originates in the MKs. Myosin is not involved in the latest stage of organelle traffic along microtubular tracks in the proplatelet shafts as shown by confocal observations of proplatelet buds. By contrast, it is required for the earlier distribution of organelles within the large MK preplatelet fragments shed into the sinusoid circulation before terminal proplatelet remodeling. We show here that F-actin is abnormally clustered in the cytoplasm of Myh9(-/-) MKs and actin polymerization is impaired in platelets. Myosin IIA is required for normal granule motility and positioning within MKs, mechanisms that may be dependent on organelle traveling and tethering onto F-actin cytoskeleton tracks. Altogether, our results indicate that the distribution of organelles within platelets critically depends on a homogeneous organelle distribution within MKs and preplatelet fragments, which requires myosin IIA.
Unité Mixte de Recherche S949, Institut National de la Santé et de la Recherche Médicale-Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg, France.
Fabien
F
Pertuy
Anita
A
Eckly
Josiane
J
Weber
Fabienne
F
Proamer
Jean-Yves
JY
Rinckel
François
F
Lanza
Christian
C
Gachet
Catherine
C
Léon
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D018715:Microscopy, Video; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D015388:Organelles / Q000502:physiology*; D013921:Thrombocytopenia / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D000199:Actins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C525088:Myh9 protein, mouse; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains