PMID- 15073148 OWN - NLM STAT- MEDLINE DCOM- 20040702 LR - 20191210 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 131 IP - 9 DP - 2004 May TI - Conversion of cell movement responses to Semaphorin-1 and Plexin-1 from attraction to repulsion by lowered levels of specific RAC GTPases in C. elegans. PG - 2073-88 AB - Plexins are functional receptors for Semaphorin axon guidance cues. Previous studies have established that some Plexins directly bind RAC(GTP) and RHO. Recent work in C. elegans showed that semaphorin 1 (smp-1 and smp-2) and plexin 1 (plx-1) are required to prevent anterior displacement of the ray 1 cells in the male tail (Fujii et al., 2002; Ginzburg et al., 2002). We show genetically that plx-1 is part of the same functional pathway as smp-1 and smp-2 for male ray positioning. RAC GTPase genes mig-2 and ced-10 probably function redundantly, whereas unc-73, which encodes a GEF for both of these GTPases, is required cell autonomously for preventing anterior displacement of ray 1 cells. RNAi analysis indicates that rho-1-encoded RHO GTPase, plus let-502 and K08B12.5-encoded RHO-kinases, are also required to prevent anterior displacement of ray 1 cells, suggesting that different kinds of RHO-family GTPases act similarly in ray 1 positioning. At low doses of wild-type mig-2 and ced-10, the Semaphorin 1 proteins no longer act through PLX-1 to prevent anterior displacements of ray 1, but have the opposite effect, acting through PLX-1 to mediate anterior displacements of ray 1. These results suggest that Plexin 1 senses levels of distinct RHO and RAC GTPases. At normal levels of RHO and RAC, Semaphorin 1 proteins and PLX-1 prevent a forward displacement of ray 1 cells, whereas at low levels of cycling RAC, Semaphorin 1 proteins and PLX-1 actively mediate their anterior displacement. Endogenously and ectopically expressed SMP-1 and SMP-2 suggest that the hook, a major source of Semaphorin 1 proteins in the male tail, normally attracts PLX-1-expressing ray 1 cells. FAU - Dalpe, Gratien AU - Dalpe G AD - Samuel Lunenfeld Research Institute of Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Canada. FAU - Zhang, Lijia W AU - Zhang LW FAU - Zheng, Hong AU - Zheng H FAU - Culotti, Joseph G AU - Culotti JG LA - eng GR - NS41397/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040408 PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Cell Adhesion Molecules) RN - 0 (Nerve Tissue Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Semaphorins) RN - 0 (plexin) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - *Body Patterning MH - COS Cells MH - Caenorhabditis elegans/anatomy & histology/*metabolism MH - Caenorhabditis elegans Proteins/genetics/*metabolism MH - Cell Adhesion Molecules/genetics/*metabolism MH - Cell Movement/*physiology MH - Chlorocebus aethiops MH - Genes, Reporter MH - Male MH - Molecular Sequence Data MH - Nerve Tissue Proteins/genetics/*metabolism MH - Protein Biosynthesis MH - RNA Interference MH - Recombinant Fusion Proteins/genetics/metabolism MH - Semaphorins/genetics/*metabolism MH - Sequence Alignment MH - Signal Transduction/physiology MH - Transcription, Genetic MH - Transgenes MH - rac GTP-Binding Proteins/*metabolism MH - rho GTP-Binding Proteins/genetics/metabolism EDAT- 2004/04/10 05:00 MHDA- 2004/07/03 05:00 CRDT- 2004/04/10 05:00 PHST- 2004/04/10 05:00 [pubmed] PHST- 2004/07/03 05:00 [medline] PHST- 2004/04/10 05:00 [entrez] AID - dev.01063 [pii] AID - 10.1242/dev.01063 [doi] PST - ppublish SO - Development. 2004 May;131(9):2073-88. doi: 10.1242/dev.01063. Epub 2004 Apr 8.