Ablation of nonmuscle myosin II-B and II-C reveals a role for nonmuscle myosin II in cardiac myocyte karyokinesis.
Ablation of nonmuscle myosin (NM) II-A or NM II-B results in mouse embryonic lethality. Here, we report the results of ablating NM II-C as well as NM II-C/II-B together in mice. NM II-C ablated mice survive to adulthood and show no obvious defects compared with wild-type littermates. However, ablation of NM II-C in mice expressing only 12% of wild-type amounts of NM II-B results in a marked increase in cardiac myocyte hypertrophy compared with the NM II-B hypomorphic mice alone. In addition, these hearts develop interstitial fibrosis associated with diffuse N-cadherin and β-catenin localization at the intercalated discs, where both NM II-B and II-C are normally concentrated. When both NM II-C and II-B are ablated the B-C-/B-C- cardiac myocytes show major defects in karyokinesis. More than 90% of B-C-/B-C- myocytes demonstrate defects in chromatid segregation and mitotic spindle formation accompanied by increased stability of microtubules and abnormal formation of multiple centrosomes. This requirement for NM II in karyokinesis is further demonstrated in the HL-1 cell line derived from mouse atrial myocytes, by using small interfering RNA knockdown of NM II or treatment with the myosin inhibitor blebbistatin. Our study shows that NM II is involved in regulating cardiac myocyte karyokinesis by affecting microtubule dynamics.
Ma
Xuefei
X
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1583, USA. max@nhlbi.nih.gov
Jana
Siddhartha S
SS
Conti
Mary Anne
MA
Kawamoto
Sachiyo
S
Claycomb
William C
WC
Adelstein
Robert S
RS
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D048750:Cell Nucleus Division / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D005260:Female; D019073:HT29 Cells; D006367:HeLa Cells; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
C483905:Myh14 protein, mouse; D024462:Myosin Type II; D024501:Nonmuscle Myosin Type IIB; D018995:Myosin Heavy Chains