title: Involvement of protein kinase C in nuclear migration during compaction and the mechanism of the migration: analyses in two-cell mouse embryos.
abstract: Compaction and nuclear migration occur in mouse embryos at the late eight-cell stage. It has been reported that activators of protein kinase C (PKC) increase adhesion of cells at the two-cell, four-cell, and uncompacted eight-cell stage. We report here that nuclear migration followed the increased adhesion of cells in such embryos when they were treated with PKC activators. These cellular events resembled those in normal embryos at the late eight-cell stage and were blocked by sphingosine, a PKC inhibitor. The responses were proportional to the dose of the PKC activator. Molecular analogues of the PKC activators, which do not affect PKC, did not induce these events. These results suggest an important role for PKC in initiation of nuclear migration as well as in compaction. Experiments were also conducted to identify the source of the mechanical force that moves the nucleus. Nuclear migration was suppressed in embryos pretreated with colchicine. Calmodulin is known to have effects on Ca(2+)-induced assembly and disassembly of microtubules. The calmodulin antagonists W-7 and W-5 suppressed nuclear migration. These results suggest that microtubules are essential for the migration and that nuclei are migrated via the Ca(2+)-induced, calmodulin-mediated assembly and disassembly of the microtubule networks. Together, these results obtained with PKC activators/inhibitor, colchicine, and calmodulin antagonists suggest that nuclear migration is mediated by increases in PKC activity, requires intact microtubules, and is accompanied by PKC-dependent increases in cell-cell adhesion.
authors.affiliation: Department of Anatomy, Mie University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohsugi
authors.forename: T
authors.initials: T
authors.lastname: Ohsawa
authors.forename: H
authors.initials: H
authors.lastname: Yamamura
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D003433:Crosses, Genetic; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013480:Superovulation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate