Galpha13 activation rescues moesin-depletion induced apoptosis in F9 teratocarcinoma cells.
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.
Krawetz
Roman
R
Department of Biology, Molecular Genetics Unit, University of Western Ontario, London, ON, Canada N6A 5B7.
MacKenzie
Michael J
MJ
Sun
Qizhi
Q
Walton
Paul A
PA
Kelly
Gregory M
GM
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
D000199:Actins; D008840:Microfilament Proteins; D016372:RNA, Antisense; D051176:beta Catenin; C071058:moesin; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D018021:Lithium Chloride