title: Probing the role of septins in cardiomyocytes.
abstract: Heart growth in the embryo is achieved by division of differentiated cardiomyocytes. Around birth, cardiomyocytes stop dividing and heart growth occurs only by volume increase of the individual cells. Cardiomyocytes seem to lose their capacity for cytokinesis at this developmental stage. Septins are GTP-binding proteins that have been shown to be involved in cytokinesis from yeast to vertebrates. We wanted to determine whether septin expression patterns can be correlated to the cessation of cytokinesis during heart development. We found significant levels of expression only for SEPT2, SEPT6, SEPT7 and SEPT9 in heart, in a developmentally regulated fashion, with high levels in the embryonic heart, downregulation around birth and no detectable expression in the adult. In dividing embryonic cardiomyocytes, all septins localize to the cleavage furrow. We used drugs to probe for the functional interactions of SEPT2 in dividing embryonic cardiomyocytes. Differences in the effects on subcellular septin localization in cardiomyocytes were observed, depending whether a Rho kinase (ROCK) inhibitor was used or whether actin and myosin were targeted directly. Our data show a tight correlation of high levels of septin expression and the ability to undergo cytokinesis in cardiomyocytes. In addition, we were able to dissect the different contributions of ROCK signaling and the actomyosin cytoskeleton to septin localization to the contractile ring using cardiomyocytes as an experimental system.
authors.affiliation: Institute of Cell Biology, ETH Zurich-Honggerberg, CH-8093 Zurich, Switzerland.
authors.forename: Preeti
authors.initials: P
authors.lastname: Ahuja
authors.forename: Evelyne
authors.initials: E
authors.lastname: Perriard
authors.forename: William
authors.initials: W
authors.lastname: Trimble
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Perriard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
mesh_terms: D000185:Actinin / Q000032:analysis / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D048749:Cytokinesis / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000032:analysis / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D029702:Schizosaccharomyces pombe Proteins; D058112:Septins; D008941:Spindle Apparatus / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D000577:Amides; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D011725:Pyridines; D029702:Schizosaccharomyces pombe Proteins; C119785:Septin9 protein, rat; D014157:Transcription Factors; C061178:cdc10 protein, S pombe; D000185:Actinin; C108830:Y 27632; C472645:blebbistatin; D015638:Cytochalasin D; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D024501:Nonmuscle Myosin Type IIB; C106863:Sept2 protein, mouse; C486672:Sept6 protein, mouse; C512895:Sept7 protein, mouse; C512894:Septin7 protein, rat; D058112:Septins