Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling.
Switching between attractive and repulsive migration in cell movement in response to extracellular guidance cues has been found in various cell types and is an important cellular function for translocation during cellular and developmental processes. Here we show that the preferential direction of migration during electrotaxis in Dictyostelium cells can be reversed by genetically modulating both guanylyl cyclases (GCases) and the cyclic guanosine monophosphate (cGMP)-binding protein C (GbpC) in combination with the inhibition of phosphatidylinositol-3-OH kinases (PI3Ks). The PI3K-dependent pathway is involved in cathode-directed migration under a direct-current electric field. The catalytic domains of soluble GCase (sGC) and GbpC also mediate cathode-directed signaling via cGMP, whereas the N-terminal domain of sGC mediates anode-directed signaling in conjunction with both the inhibition of PI3Ks and cGMP production. These observations provide an identification of the genes required for directional switching in electrotaxis and suggest that a parallel processing of electric signals, in which multiple-signaling pathways act to bias cell movement toward the cathode or anode, is used to determine the direction of migration.
Laboratories for Nanobiology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Masayuki J
MJ
Sato
Hidekazu
H
Kuwayama
Wouter N
WN
van Egmond
Airi L K
AL
Takayama
Hiroaki
H
Takagi
Peter J M
PJ
van Haastert
Toshio
T
Yanagida
Masahiro
M
Ueda
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D006152:Cyclic GMP / Q000494:pharmacology*; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D004560:Electricity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000737:chemistry; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010716:Phosphatidylinositols / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D006162:Guanylate Cyclase; D006152:Cyclic GMP