CGEF-1 and CHIN-1 regulate CDC-42 activity during asymmetric division in the Caenorhabditis elegans embryo.
The anterior-posterior axis of the Caenorhabditis elegans embryo is elaborated at the one-cell stage by the polarization of the partitioning (PAR) proteins at the cell cortex. Polarization is established under the control of the Rho GTPase RHO-1 and is maintained by the Rho GTPase CDC-42. To understand more clearly the role of the Rho family GTPases in polarization and division of the early embryo, we constructed a fluorescent biosensor to determine the localization of CDC-42 activity in the living embryo. A genetic screen using this biosensor identified one positive (putative guanine nucleotide exchange factor [GEF]) and one negative (putative GTPase activating protein [GAP]) regulator of CDC-42 activity: CGEF-1 and CHIN-1. CGEF-1 was required for robust activation, whereas CHIN-1 restricted the spatial extent of CDC-42 activity. Genetic studies placed CHIN-1 in a novel regulatory loop, parallel to loop described previously, that maintains cortical PAR polarity. We found that polarized distributions of the nonmuscle myosin NMY-2 at the cell cortex are independently produced by the actions of RHO-1, and its effector kinase LET-502, during establishment phase and CDC-42, and its effector kinase MRCK-1, during maintenance phase. CHIN-1 restricted NMY-2 recruitment to the anterior during maintenance phase, consistent with its role in polarizing CDC-42 activity during this phase.
Kumfer
Kraig T
KT
Laboratorie of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA. kumfer@gmail.com
Cook
Steven J
SJ
Squirrell
Jayne M
JM
Eliceiri
Kevin W
KW
Peel
Nina
N
O'Connell
Kevin F
KF
White
John G
JG
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D016764:Cell Polarity; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D024462:Myosin Type II / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
C547940:CGEF-1 protein, C elegans; C547941:CHIN-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D049452:Green Fluorescent Proteins; D024462:Myosin Type II; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins