PMID- 19346484 OWN - NLM STAT- MEDLINE DCOM- 20090529 LR - 20211020 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 106 IP - 16 DP - 2009 Apr 21 TI - Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling. PG - 6667-72 LID - 10.1073/pnas.0809974106 [doi] AB - 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. FAU - Sato, Masayuki J AU - Sato MJ AD - Laboratories for Nanobiology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan. FAU - Kuwayama, Hidekazu AU - Kuwayama H FAU - van Egmond, Wouter N AU - van Egmond WN FAU - Takayama, Airi L K AU - Takayama AL FAU - Takagi, Hiroaki AU - Takagi H FAU - van Haastert, Peter J M AU - van Haastert PJ FAU - Yanagida, Toshio AU - Yanagida T FAU - Ueda, Masahiro AU - Ueda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090403 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Enzyme Inhibitors) RN - 0 (Phosphatidylinositols) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - EC 4.6.1.2 (Guanylate Cyclase) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Animals MH - Cell Movement/*drug effects MH - Cyclic GMP/*pharmacology MH - Dictyostelium/*cytology/*drug effects/enzymology MH - *Electricity MH - Enzyme Inhibitors/pharmacology MH - Guanylate Cyclase/antagonists & inhibitors/chemistry MH - Intracellular Space/drug effects/metabolism MH - Models, Biological MH - Mutation/genetics MH - Phosphatidylinositols/*pharmacology MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Structure, Tertiary MH - Protein Transport/drug effects MH - Signal Transduction/*drug effects PMC - PMC2672521 COIS- The authors declare no conflict of interest. EDAT- 2009/04/07 09:00 MHDA- 2009/05/30 09:00 PMCR- 2009/10/21 CRDT- 2009/04/07 09:00 PHST- 2009/04/07 09:00 [entrez] PHST- 2009/04/07 09:00 [pubmed] PHST- 2009/05/30 09:00 [medline] PHST- 2009/10/21 00:00 [pmc-release] AID - 0809974106 [pii] AID - 7521 [pii] AID - 10.1073/pnas.0809974106 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6667-72. doi: 10.1073/pnas.0809974106. Epub 2009 Apr 3.