Anillin localization defect in cardiomyocyte binucleation.
Heart growth is augmented during early development by cardiomyocyte proliferation. In contrast, heart growth during postnatal life occurs by increasing cell size. Postnatal cardiomyocytes can undergo DNA synthesis, mitosis and binucleation. However, they lose the ability to complete cytokinesis. The underlying mechanism is poorly understood. It has been suggested that incomplete disassembly of contractile elements prohibits cytokinesis. Here, we show that serum-induced binucleation results in the normal disassembly of the contractile apparatus. In contrast, analysis of Aurora B and Anillin localization demonstrates that binucleation is characterized by asymmetric constriction, delay of furrow constriction and defective mid-body formation. Anillin fails to focus at the cortex in anaphase and shows an expanded localization around the mid-body during cytokinesis. p38 inhibition rescues the mid-body formation defect. We show that p38 accumulates during cytokinesis at the mid-body and suggest that p38 activity has a regulatory role in cytokinesis. Microarray analysis reveals that p38 inhibition upregulates core components of the central spindle. Taken together, our results demonstrate that postnatal cardiomyocytes form a cleavage furrow and that binucleation is associated with an Anillin localization defect.
Engel
Felix B
FB
Department of Pediatrics, Harvard Medical School, and Department of Cardiology, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA. engel@enders.tch.harvard.edu
Schebesta
Michael
M
Keating
Mark T
MT
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002455:Cell Division; D002467:Cell Nucleus / Q000473:pathology*; D049109:Cell Proliferation; D002875:Chromosomes / Q000502:physiology; D003285:Contractile Proteins / Q000378:metabolism*; D048749:Cytokinesis; D005786:Gene Expression Regulation; D008938:Mitosis; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D003285:Contractile Proteins; C095886:anillin; C576925:Aurkb protein, rat; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases