Distinct localizations and roles of non-muscle myosin II during proplatelet formation and platelet release.
BACKGROUND
At the end of maturation, megakaryocytes (MKs) form long cytoplasmic extensions called proplatelets (PPT). Enormous changes in cytoskeletal structures cause PPT to extend further, to re-localize organelles such as mitochondria and to fragment, leading to platelet release. Two non-muscle myosin IIs (NMIIs) are expressed in MKs; however, only NMII-A (MYH9), but not NMII-B (MYH10), is expressed in mature MKs and is implicated in PPT formation.


OBJECTIVE
To provide in vivo evidence on the specific role of NMII-A and IIB in MK PPT formation.


METHODS
We studied two transgenic mouse models in which non-muscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B.


CONCLUSIONS
This work demonstrates that the kinetic properties of NM-IIA, depending on the N-terminal domain, render NMII-A the better NMII candidate to control PPT formation. Furthermore, the carboxyl-terminal domain determines myosin II localization in the constriction region of PPT and is responsible for the specific role of NMII in platelet release.
Institut National de la Santé et de la Recherche Médicale, Villejuif, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France.
I
I
Badirou
J
J
Pan
S
S
Souquere
C
C
Legrand
G
G
Pierron
A
A
Wang
A
A
Eckly
A
A
Roy
C
C
Gachet
W
W
Vainchenker
Y
Y
Chang
C
C
Léon
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D024462:Myosin Type II / Q000378:metabolism*
D024462:Myosin Type II
Non-muscle myosin type IIA; Non-muscle myosin type IIB; megakaryocyte; platelet; stem cell