Goα regulates olfactory adaptation by antagonizing Gqα-DAG signaling in Caenorhabditis elegans

The heterotrimeric G protein Go is abundantly expressed in the mammalian nervous system and modulates neural activities in response to various ligands. However, Go's functions in living animals are less well understood. Here, we demonstrate that GOA-1 Goα has a fundamental role in olfactory adaptation in Caenorhabditis elegans. Impairment of GOA-1 Goα function and excessive activation of EGL-30 Gqα cause a defect in adaptation to AWC-sensed odorants. These pathways antagonistically modulate olfactory adaptation in AWC chemosensory neurons. Wild-type animals treated with phorbol esters and double-mutant animals of diacylglycerol (DAG) kinases, dgk-3; dgk-1, also have a defect in adaptation, suggesting that elevated DAG signals disrupt normal adaptation. Constitutively active GOA-1 can suppress the adaptation defect of dgk-3; dgk-1 double mutants, whereas it fails to suppress the adaptation defect of animals with constitutively active EGL-30, implying that GOA-1 acts upstream of EGL-30 in olfactory adaptation. Our results suggest that down-regulation of EGL-30–DAG signaling by GOA-1 underlies olfactory adaptation and plasticity of chemotaxis.

[1]  Michael R Koelle,et al.  Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans , 2004, Nature Neuroscience.

[2]  J. Vincent,et al.  Dopamine depresses synaptic inputs into the olfactory bulb. , 1999, Journal of neurophysiology.

[3]  I. Mori,et al.  Negative Regulation and Gain Control of Sensory Neurons by the C. elegans Calcineurin TAX-6 , 2002, Neuron.

[4]  J. Kaplan,et al.  Facilitation of Synaptic Transmission by EGL-30 Gqα and EGL-8 PLCβ DAG Binding to UNC-13 Is Required to Stimulate Acetylcholine Release , 1999, Neuron.

[5]  R. Anholt,et al.  Differential expression of G proteins in the mouse olfactory system , 1999, Brain Research.

[6]  D. Wilson,et al.  Habituation of odor responses in the rat anterior piriform cortex. , 1998, Journal of neurophysiology.

[7]  S. Brenner.  The genetics of Caenorhabditis elegans. , 1974, Genetics.

[8]  Aravinthan D. T. Samuel,et al.  Identification of Thermosensory and Olfactory Neuron-Specific Genes via Expression Profiling of Single Neuron Types , 2004, Current Biology.

[9]  Jeremy Mendel,et al.  Participation of the protein Go in multiple aspects of behavior in C. elegans , 1995, Science.

[10]  A. Jose,et al.  Domains, Amino Acid Residues, and New Isoforms of Caenorhabditis elegans Diacylglycerol Kinase 1 (DGK-1) Important for Terminating Diacylglycerol Signaling in Vivo* , 2005, Journal of Biological Chemistry.

[11]  G. Ruvkun,et al.  Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  L. Avery,et al.  Mutations in a C. elegans Gqα Gene Disrupt Movement, Egg Laying, and Viability , 1996, Neuron.

[13]  Takaaki Hirotsu,et al.  Neural circuit‐dependent odor adaptation in C. elegans is regulated by the Ras‐MAPK pathway , 2005, Genes to cells : devoted to molecular & cellular mechanisms.

[14]  Stephan L. Chorover,et al.  Response plasticity in hamster olfactory bulb: peripheral and central processes , 1976, Brain Research.

[15]  Cori Bargmann,et al.  Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans , 1995, Cell.

[16]  Cori Bargmann,et al.  The Gα Protein ODR-3 Mediates Olfactory and Nociceptive Function and Controls Cilium Morphogenesis in C. elegans Olfactory Neurons , 1998, Neuron.

[17]  E. Cuppen,et al.  Proteins Interacting With Caenorhabditis elegans  Gα Subunits , 2003, Comparative and functional genomics.

[18]  Cornelia I Bargmann,et al.  Reprogramming Chemotaxis Responses: Sensory Neurons Define Olfactory Preferences in C. elegans , 1997, Cell.

[19]  D. van der Kooy,et al.  Serotonin mediates food-odor associative learning in the nematode Caenorhabditis elegans , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  I. Mori,et al.  Neural regulation of thermotaxis in Caenorhabditis elegans , 1995, Nature.

[21]  Cornelia I. Bargmann,et al.  Olfaction and Odor Discrimination Are Mediated by the C. elegans Guanylyl Cyclase ODR-1 , 2000, Neuron.

[22]  J. Kaplan,et al.  Serotonin Inhibition of Synaptic Transmission Gαo Decreases the Abundance of UNC-13 at Release Sites , 1999, Neuron.

[23]  Koutarou D. Kimura,et al.  Diverse regulation of sensory signaling by C. elegans nPKC‐epsilon/eta TTX‐4 , 2005, The EMBO journal.

[24]  L. Avery,et al.  The genetics of feeding in Caenorhabditis elegans. , 1993, Genetics.

[25]  H. Horvitz,et al.  EGL-10 Regulates G Protein Signaling in the C. elegans Nervous System and Shares a Conserved Domain with Many Mammalian Proteins , 1996, Cell.

[26]  P. Trombley,et al.  Dopaminergic modulation at the olfactory nerve synapse , 2000, Brain Research.

[27]  J. Bessereau,et al.  [C. elegans: of neurons and genes]. , 2003, Medecine sciences : M/S.

[28]  E. Cuppen,et al.  The G-protein beta-subunit GPB-2 in Caenorhabditis elegans regulates the G(o)alpha-G(q)alpha signaling network through interactions with the regulator of G-protein signaling proteins EGL-10 and EAT-16. , 2001, Genetics.

[29]  L. Ségalat,et al.  Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans , 1995, Science.

[30]  F. Zufall,et al.  The cellular and molecular basis of odor adaptation. , 2000, Chemical senses.

[31]  P. Sternweis,et al.  Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. , 1984, The Journal of biological chemistry.

[32]  K. Miller,et al.  Convergent, RIC-8-Dependent Gα Signaling Pathways in the Caenorhabditis elegans Synaptic Signaling Network , 2005, Genetics.

[33]  Cori Bargmann,et al.  Odorant-selective genes and neurons mediate olfaction in C. elegans , 1993, Cell.

[34]  Cori Bargmann,et al.  The Cyclic GMP-Dependent Protein Kinase EGL-4 Regulates Olfactory Adaptation in C. elegans , 2002, Neuron.

[35]  R. Plasterk,et al.  The complete family of genes encoding G proteins of Caenorhabditis elegans , 1999, Nature Genetics.

[36]  G. Patikoglou,et al.  Two RGS proteins that inhibit Gαo and Gαq signaling in C. elegans neurons require a Gβ5-like subunit for function , 2001, Current Biology.

[37]  P. Sternberg,et al.  Antagonism between Goα and Gqα in Caenorhabditis elegans: the RGS protein EAT-16 is necessary for Goα signaling and regulates Gqα activity , 1999 .

[38]  K. Miller,et al.  Goα and Diacylglycerol Kinase Negatively Regulate the Gqα Pathway in C. elegans , 1999, Neuron.

[39]  O. Hobert,et al.  Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. , 2003, Journal of neurobiology.

[40]  M. Yamamoto,et al.  Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. , 2001, The Journal of experimental biology.

[41]  D. van der Kooy,et al.  Regulation of distinct attractive and aversive mechanisms mediating benzaldehyde chemotaxis in Caenorhabditis elegans. , 2001, Learning & memory.

[42]  M. Peyton,et al.  Multiple neurological abnormalities in mice deficient in the G protein Go. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  L. Avery,et al.  Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Cornelia I Bargmann,et al.  Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans , 1995, Neuron.

[45]  M. T. Shipley,et al.  Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals. , 2001, Journal of neurophysiology.

[46]  Cori Bargmann,et al.  OSM-9, A Novel Protein with Structural Similarity to Channels, Is Required for Olfaction, Mechanosensation, and Olfactory Adaptation inCaenorhabditis elegans , 1997, The Journal of Neuroscience.

[47]  T. Ishihara,et al.  TBX2/TBX3 transcriptional factor homologue controls olfactory adaptation in Caenorhabditis elegans. , 2004, Journal of neurobiology.

[48]  R. Anholt,et al.  Impaired olfactory behavior in mice deficient in the α subunit of Go , 2002, Brain Research.

[49]  M. T. Shipley,et al.  Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA(B) heteroreceptors. , 2000, Journal of neurophysiology.

[50]  Leon Avery,et al.  eat-11 encodes GPB-2, a Gβ5 ortholog that interacts with Goα and Gqα to regulate C. elegans behavior , 2001, Current Biology.

[51]  J. Benovic,et al.  Caenorhabditus elegans Arrestin Regulates Neural G Protein Signaling and Olfactory Adaptation and Recovery* , 2005, Journal of Biological Chemistry.

[52]  M. Nonet,et al.  Resistance to Volatile Anesthetics by Mutations Enhancing Excitatory Neurotransmitter Release in Caenorhabditis elegans , 2004, Genetics.