title: Galpha13 activation rescues moesin-depletion induced apoptosis in F9 teratocarcinoma cells.
abstract: Mouse F9 cells differentiate into primitive endoderm when treated with retinoic acid (RA) and into parietal endoderm in response to RA and dibutyryl (db-) cAMP. G protein signaling either blocks or mimics RA-induced differentiation, the latter signaling through the Wnt-beta-catenin pathway. In our study, we found that a constitutively active Galpha13 mutant induces F9 cells to differentiate into parietal endoderm in the absence of exogenous agents. Galpha13 expression and subsequent differentiation are accompanied by beta-catenin translocation to the nucleus. Differentiation and changes in cell morphology are supported by rearrangements to the F-actin cytoskeleton. ERM (ezrin-radixin-moesin) proteins, known to link F-actin to transmembrane receptors, are also redistributed during differentiation. Furthermore, morpholino antisense and shRNA approaches show that moesin expression is essential since its knockdown leads to altered F-actin distribution and subsequent apoptosis. Moesin-depleted cells, however, remain attached to the substrate when Galpha13 is constitutively expressed, but they do not differentiate into extraembryonic endoderm. Our study demonstrates a link between Galpha13 signaling that regulates differentiation of F9 cells through primitive to parietal endoderm and a moesin requirement for cell survival.
authors.affiliation: Department of Biology, Molecular Genetics Unit, University of Western Ontario, London, ON, Canada N6A 5B7.
authors.forename: Roman
authors.initials: R
authors.lastname: Krawetz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacKenzie
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Sun
authors.forename: Paul A
authors.initials: PA
authors.lastname: Walton
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Kelly
mesh_terms: D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004707:Endoderm / Q000166:cytology*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D016372:RNA, Antisense / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D016372:RNA, Antisense; D051176:beta Catenin; C071058:moesin; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D018021:Lithium Chloride