Abstract
Heterotrimeric G proteins promote microtubule forces that position mitotic spindles during asymmetric cell division in C. elegans embryos. While all previously studied G protein functions require activation by seven-transmembrane receptors, this function appears to be receptor independent. We found that mutating a regulator of G protein signaling, RGS-7, resulted in hyperasymmetric spindle movements due to decreased force on one spindle pole. RGS-7 is localized at the cell cortex, and its effects require two redundant Galphao-related G proteins and their nonreceptor activators RIC-8 and GPR-1/2. Using recombinant proteins, we found that RIC-8 stimulates GTP binding by Galphao and that the RGS domain of RGS-7 stimulates GTP hydrolysis by Galphao, demonstrating that Galphao passes through the GTP bound state during its activity cycle. While GTPase activators typically inactivate G proteins, RGS-7 instead appears to promote G protein function asymmetrically in the cell, perhaps acting as a G protein effector.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Division / physiology
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Centrosome / metabolism
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Embryo, Nonmammalian / anatomy & histology
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Embryo, Nonmammalian / physiology
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GTP-Binding Protein alpha Subunits / metabolism
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Guanine Nucleotide Exchange Factors
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Guanosine Triphosphate / metabolism
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Mutation
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Nuclear Proteins / metabolism
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Protein Binding
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RGS Proteins / genetics
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RGS Proteins / metabolism*
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RNA Interference
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Spindle Apparatus / metabolism*
Substances
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Caenorhabditis elegans Proteins
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G protein regulator 1, C elegans
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G protein regulator 2, C elegans
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GTP-Binding Protein alpha Subunits
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Guanine Nucleotide Exchange Factors
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Nuclear Proteins
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RGS Proteins
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RIC-8 protein, C elegans
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Recombinant Fusion Proteins
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rgs-7 protein, C elegans
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Guanosine Triphosphate
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Heterotrimeric GTP-Binding Proteins