Glycogen synthase kinase-3 is required for efficient Dictyostelium chemotaxis.
Glycogen synthase kinase-3 (GSK3) is a highly conserved protein kinase that is involved in several important cell signaling pathways and is associated with a range of medical conditions. Previous studies indicated a major role of the Dictyostelium homologue of GSK3 (gskA) in cell fate determination during morphogenesis of the fruiting body; however, transcriptomic and proteomic studies have suggested that GSK3 regulates gene expression much earlier during Dictyostelium development. To investigate a potential earlier role of GskA, we examined the effects of loss of gskA on cell aggregation. We find that cells lacking gskA exhibit poor chemotaxis toward cAMP and folate. Mutants fail to activate two important regulatory signaling pathways, mediated by phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and target of rapamycin complex 2 (TORC2), which in combination are required for chemotaxis and cAMP signaling. These results indicate that GskA is required during early stages of Dictyostelium development, in which it is necessary for both chemotaxis and cell signaling.
Teo
Regina
R
Cardiff School of Biosciences, Cardiff University, CF10 3AX Cardiff, United Kingdom. teor@cardiff.ac.uk
Lewis
Kimberley J
KJ
Forde
Josephine E
JE
Ryves
W Jonathan
WJ
Reddy
Jonathan V
JV
Rogers
Benjamin J
BJ
Harwood
Adrian J
AJ
D002449:Cell Aggregation / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D005492:Folic Acid / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D010716:Phosphatidylinositols; D015800:Protozoan Proteins; C118303:phosphoinositide-3,4,5-triphosphate; D005492:Folic Acid; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase