Regulation of cell adhesion during embryonic compaction of mammalian embryos: roles for PKC and beta-catenin.
Beta-catenin has a number of roles in early development including involvement in cell adhesion, cell signaling, and developmental fate specification. This study investigates the mechanisms that regulate embryonic compaction, the first cell adhesion event in early mammalian development. Mammalian embryos can be induced to compact at an earlier developmental stage than normal by treatment with agonists that activate protein kinase C (PKC), and this treatment is used to identify and analyze the minimum essential changes required for embryonic compaction. It was predicted that: (1) since activation of PKC can induce compaction prematurely in mouse embryos, phosphorylation of the protein components of the adherens complex would occur during induced compaction and that these components would be required for the cell adhesive event; (2) these same proteins should be phosphorylated during compaction in normal development; (3) new, highly-specific inhibitors of PKC activity would inhibit compaction during normal development and induced compaction; and (4) some PKC isotypes would become localized to the junctional membranes during the process of compaction. In agreement with these predictionst, beta-catenin became phosphorylated on serine/threonine residues both during induced compaction and normal development. Inhibitors to PKC, but not inhibitors to other kinases, blocked compaction. Furthermore, the alpha isotype of PKC is recruited to the membranes of the apposing blastomeres both during induced compaction and during normal development immediately before compaction begins and before beta-catenin becomes part of the detergent-resistant cytoskeleton at the junction.
Pauken
C M
CM
Molecular and Cellular Biology Program/Biology, Arizona State University, Tempe, Arizona 85287-1510, USA.
Capco
D G
DG
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051180:Desmoplakins; D004622:Embryo, Mammalian / Q000201:enzymology / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D011493:Protein Kinase C