16 results on '"Stauffer, Anna M."'
Search Results
2. Selective Manipulation of G-Protein γ7 Subunit in Mice Provides New Insights into Striatal Control of Motor Behavior.
- Author
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Brunori, Gloria, Pelletier, Oliver B., Stauffer, Anna M., and Robishaw, Janet D.
- Subjects
CELL physiology ,CELLULAR signal transduction ,LABORATORY mice ,ADENYLATE cyclase - Abstract
Stimulatory coupling of dopamine D1 (D1R) and adenosine A2A receptors (A2AR) to adenylyl cyclase within the striatum is mediated through a specific Gαolfβ2γ7 heterotrimer to ultimately modulate motor behaviors. To dissect the individual roles of the Gαolfβ2γ7 heterotrimer in different populations of medium spiny neurons (MSNs), we produced and characterized conditional mouse models, in which the Gng7 gene was deleted in either the D1R-or A2AR/D2R-expressing MSNs. We show that conditional loss of γ7 disrupts the cell type-specific assembly of the Gαolfβ2γ7 heterotrimer, thereby identifying its circumscribed roles acting downstream of either the D1Rs or A2ARs in coordinating motor behaviors, including in vivo responses to psychostimulants. We reveal that Gαolfβ2γ7/cAMP signal in D1R-MSNs does not impact spontaneous and amphetamine-induced locomotor behaviors in male and female mice, while its loss in A2AR/D2R-MSNs results in a hyperlocomotor phenotype and enhanced locomotor response to amphetamine. Additionally, Gαolfβ2γ7/cAMP signal in either D1R- or A2AR/D2R-expressing MSNs is not required for the activation of PKA signaling by amphetamine. Finally, we show that Gαolfβ2γ7 signaling acting downstream of D1Rs is selectively implicated in the acute locomotor-enhancing effects of morphine. Collectively, these results support the general notion that receptors use specific Gαβγ proteins to direct the fidelity of downstream signaling pathways and to elicit a diverse repertoire of cellular functions. Specifically, these findings highlight the critical role for the γ7 protein in determining the cellular level, and hence, the function of the Gαolfβ2γ7 heterotrimer in several disease states associated with dysfunctional striatal signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. Disruption of G-Protein γ5 Subtype Causes Embryonic Lethality in Mice
- Author
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Moon, Anne M., primary, Stauffer, Anna M., additional, Schwindinger, William F., additional, Sheridan, Kathy, additional, Firment, Ashley, additional, and Robishaw, Janet D., additional
- Published
- 2014
- Full Text
- View/download PDF
4. Synergistic Roles for G-protein γ3 and γ7 Subtypes in Seizure Susceptibility as Revealed in Double Knock-out Mice
- Author
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Schwindinger, William F., primary, Mirshahi, Uyenlinh L., additional, Baylor, Kelly A., additional, Sheridan, Kathleen M., additional, Stauffer, Anna M., additional, Usefof, Stephanie, additional, Stecker, Mark M., additional, Mirshahi, Tooraj, additional, and Robishaw, Janet D., additional
- Published
- 2012
- Full Text
- View/download PDF
5. The orphan G protein-coupled receptor 161 is required for left–right patterning
- Author
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Leung, TinChung, primary, Humbert, Jasper E., additional, Stauffer, Anna M., additional, Giger, Kathryn E., additional, Chen, Hui, additional, Tsai, Huai-Jen, additional, Wang, Chuan, additional, Mirshahi, Tooraj, additional, and Robishaw, Janet D., additional
- Published
- 2008
- Full Text
- View/download PDF
6. Expression of the G protein γT1 subunit during zebrafish development
- Author
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Chen, Hui, primary, Leung, TinChung, additional, Giger, Kathryn E., additional, Stauffer, Anna M., additional, Humbert, Jasper E., additional, Sinha, Soniya, additional, Horstick, Eric J., additional, Hansen, Carl A., additional, and Robishaw, Janet D., additional
- Published
- 2007
- Full Text
- View/download PDF
7. Zebrafish G protein γ2 is required for VEGF signaling during angiogenesis
- Author
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Leung, TinChung, primary, Chen, Hui, additional, Stauffer, Anna M., additional, Giger, Kathryn E., additional, Sinha, Soniya, additional, Horstick, Eric J., additional, Humbert, Jasper E., additional, Hansen, Carl A., additional, and Robishaw, Janet D., additional
- Published
- 2006
- Full Text
- View/download PDF
8. Mice with Deficiency of G Protein γ 3 Are Lean and Have Seizures
- Author
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Schwindinger, William F., primary, Giger, Kathryn E., additional, Betz, Kelly S., additional, Stauffer, Anna M., additional, Sunderlin, Elaine M., additional, Sim-Selley, Laura J., additional, Selley, Dana E., additional, Bronson, Sarah K., additional, and Robishaw, Janet D., additional
- Published
- 2004
- Full Text
- View/download PDF
9. Disruption of G-Protein γ5 Subtype Causes Embryonic Lethality in Mice.
- Author
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Moon, Anne M., Stauffer, Anna M., Schwindinger, William F., Sheridan, Kathy, Firment, Ashley, and Robishaw, Janet D.
- Subjects
- *
LABORATORY mice , *EMBRYOLOGY , *CELL proliferation , *CELL migration , *CELL differentiation , *HEART diseases , *HEART abnormalities - Abstract
Heterotrimeric G-proteins modulate many processes essential for embryonic development including cellular proliferation, migration, differentiation, and survival. Although most research has focused on identifying the roles of the various αsubtypes, there is growing recognition that similarly divergent βγ dimers also regulate these processes. In this paper, we show that targeted disruption of the mouse Gng5 gene encoding the γ5 subtype produces embryonic lethality associated with severe head and heart defects. Collectively, these results add to a growing body of data that identify critical roles for the γ subunits in directing the assembly of functionally distinct G-αβγ trimers that are responsible for regulating diverse biological processes. Specifically, the finding that loss of the G-γ5 subtype is associated with a reduced number of cardiac precursor cells not only provides a causal basis for the mouse phenotype but also raises the possibility that G-βγ5 dependent signaling contributes to the pathogenesis of human congenital heart problems. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. Mice with Deficiency of G Protein γ3 Are Lean and Have Seizures.
- Author
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Schwindinger, Willaim F., Giger, Kathryn E., Betz, Kelly S., Stauffer, Anna M., Sunderlin, Elaine M., Sim-Selley, Laura J., Selley, Dana E., Bronson, Sarah K., and Robinshaw, Janet D.
- Subjects
ANTHROPOMETRY ,GENETICS ,MEMBRANE proteins ,PHENOTYPES ,WEIGHT gain ,BODY weight ,OBESITY - Abstract
Emerging evidence suggests that the γ subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve γ subtypes, γ
3 is abundantly and widely expressed in the brain. To identify specific functions and associations for γ3 , a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3-/- ). Confirming the efficacy and specificity of gene targeting, Gng3-/- mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for γ3 in the brain, Gng3-/- mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for γ3 , these phenotypic changes are associated with significant reductions in β2 and αi3 subunit levels in certain regions of the brain. The finding that the Gng3-/- mice and the previously reported Gng7-/- mice display distinct phenotypes and different &alphaβγ subunit associations supports the notion that even closely related γ subtypes, such as γ3 and γ7 , perform unique functions in the context of the organism. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
11. Zebrafish G protein γ2is required for VEGF signaling during angiogenesis
- Author
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Leung, TinChung, Chen, Hui, Stauffer, Anna M., Giger, Kathryn E., Sinha, Soniya, Horstick, Eric J., Humbert, Jasper E., Hansen, Carl A., and Robishaw, Janet D.
- Abstract
Vascular endothelial growth factor (VEGF) is a major mediator of pathologic angiogenesis, a process necessary for the formation of new blood vessels to support tumor growth. Historically, VEGF has been thought to signal via receptor tyrosine kinases, which are not typically considered to be G protein dependent. Here, we show that targeted knockdown of the G protein gng2gene (Gγ2) blocks the normal angiogenic process in developing zebrafish embryos. Moreover, loss of gng2function inhibits the ability of VEGF to promote the angiogenic sprouting of blood vessels by attenuating VEGF induced phosphorylation of phospholipase C-gamma1 (PLCγ1) and serine/threonine kinase (AKT). Collectively, these results demonstrate a novel interaction between Gγ2- and VEGF-dependent pathways to regulate the angiogenic process in a whole-animal model. Blocking VEGF function using a humanized anti-VEGF antibody has emerged as a promising treatment for colorectal, non-small lung cell, and breast cancers. However, this treatment may cause considerable side effects. Our findings provide a new opportunity for cotargeting G protein- and VEGF-dependent pathways to synergistically block pathologic angiogenesis, which may lead to a safer and more efficacious therapeutic regimen to fight cancer. (Blood. 2006;108:160-166)
- Published
- 2006
- Full Text
- View/download PDF
12. Synergistic Roles for G-protein γ3 and γ7 Subtypes in Seizure Susceptibility as Revealed in Double Knock-out Mice.
- Author
-
Schwindinger, William F., Mirshahi, Uyenlinh L., Baylor, Kelly A., Sheridan, Kathleen M., Stauffer, Anna M., Usefof, Stephanie, Stecker, Mark M., Mirshahi, Tooraj, and Robishaw, Janet D.
- Subjects
- *
G proteins , *LABORATORY mice , *AMINOBUTYRIC acid , *DOPAMINE receptors , *EARLY death - Abstract
The functions of different G-proteinαβγ subunit combinations are traditionally ascribed to their variousα components. However, the discovery of similarly diverse γ subtypes raises the possibility that they may also contribute to specificity. To test this possibility, we used a gene targeting approach to determine whether the closely related γ3 and γ7 subunits can perform functionally interchangeable roles in mice. In contrast to single knock-out mice that show normal survival, Gng3-/-Gng7-/- double knock-out mice display a progressive seizure disorder that dramatically reduces their median life span to only 75 days. Biochemical analyses reveal that the severe phenotype is not due to redundant roles for the two γ subunits in the same signaling pathway but rather is attributed to their unique actions in different signaling pathways. The results suggest that the γ3 subunit is a component of a Gi/o protein that is required for γ-aminobutyric acid, type B, receptor-regulated neuronal excitability, whereas the γ7 subunit is a component of a Golf protein that is responsible for A2A adenosine or D1 dopamine receptor-induced neuro-protective response. The development of this mouse model offers a novel experimental framework for exploring how signaling pathways integrate to produce normal brain function and how their combined dysfunction leads to spontaneous seizures and premature death. The results underscore the critical role of the γ subunit in this process. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
13. Selective Manipulation of G-Protein γ 7 Subunit in Mice Provides New Insights into Striatal Control of Motor Behavior.
- Author
-
Brunori G, Pelletier OB, Stauffer AM, and Robishaw JD
- Subjects
- Amphetamine pharmacology, Animals, Central Nervous System Stimulants pharmacology, Corpus Striatum drug effects, Corpus Striatum physiology, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Dopamine Agents pharmacology, Female, GTP-Binding Protein gamma Subunits genetics, Gene Deletion, Hand Strength, Male, Mice, Mice, Inbred C57BL, Receptors, Dopamine D1 metabolism, Signal Transduction, Corpus Striatum metabolism, GTP-Binding Protein gamma Subunits metabolism, Locomotion
- Abstract
Stimulatory coupling of dopamine D
1 (D1 R) and adenosine A2A receptors (A2A R) to adenylyl cyclase within the striatum is mediated through a specific Gαolf β2 γ7 heterotrimer to ultimately modulate motor behaviors. To dissect the individual roles of the Gαolf β2 γ7 heterotrimer in different populations of medium spiny neurons (MSNs), we produced and characterized conditional mouse models, in which the Gng7 gene was deleted in either the D1 R- or A2A R/D2 R-expressing MSNs. We show that conditional loss of γ7 disrupts the cell type-specific assembly of the Gαolf β2 γ7 heterotrimer, thereby identifying its circumscribed roles acting downstream of either the D1 Rs or A2A Rs in coordinating motor behaviors, including in vivo responses to psychostimulants. We reveal that Gαolf β2 γ7 /cAMP signal in D1 R-MSNs does not impact spontaneous and amphetamine-induced locomotor behaviors in male and female mice, while its loss in A2A R/D2 R-MSNs results in a hyperlocomotor phenotype and enhanced locomotor response to amphetamine. Additionally, Gαolf β2 γ7 /cAMP signal in either D1 R- or A2A R/D2 R-expressing MSNs is not required for the activation of PKA signaling by amphetamine. Finally, we show that Gαolf β2 γ7 signaling acting downstream of D1 Rs is selectively implicated in the acute locomotor-enhancing effects of morphine. Collectively, these results support the general notion that receptors use specific Gαβγ proteins to direct the fidelity of downstream signaling pathways and to elicit a diverse repertoire of cellular functions. Specifically, these findings highlight the critical role for the γ7 protein in determining the cellular level, and hence, the function of the Gαolf β2 γ7 heterotrimer in several disease states associated with dysfunctional striatal signaling. SIGNIFICANCE STATEMENT Dysfunction or imbalance of cAMP signaling in the striatum has been linked to several neurologic and neuropsychiatric disorders, including Parkinson's disease, dystonia, schizophrenia, and drug addiction. By genetically targeting the γ7 subunit in distinct striatal neuronal subpopulations in mice, we demonstrate that the formation and function of the Gαolf β2 γ7 heterotrimer, which represents the rate-limiting step for cAMP production in the striatum, is selectively disrupted. Furthermore, we reveal cell type-specific roles for Gαolf β2 γ7 -mediated cAMP production in the control of spontaneous locomotion as well as behavioral and molecular responses to psychostimulants. Our findings identify the γ7 protein as a novel therapeutic target for disease states associated with dysfunctional striatal cAMP signaling., (Copyright © 2021 the authors.)- Published
- 2021
- Full Text
- View/download PDF
14. Expression of the G protein gammaT1 subunit during zebrafish development.
- Author
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Chen H, Leung T, Giger KE, Stauffer AM, Humbert JE, Sinha S, Horstick EJ, Hansen CA, and Robishaw JD
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, GTP-Binding Protein gamma Subunits genetics, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, In Situ Hybridization, Molecular Sequence Data, Oligonucleotides, Antisense pharmacology, Otx Transcription Factors genetics, Otx Transcription Factors metabolism, Photoreceptor Cells metabolism, Pineal Gland cytology, Pineal Gland metabolism, RNA Probes, Retina cytology, Retina metabolism, Rhodopsin metabolism, Sequence Homology, Amino Acid, Trans-Activators genetics, Trans-Activators metabolism, Zebrafish growth & development, Zebrafish metabolism, Zebrafish Proteins genetics, GTP-Binding Protein gamma Subunits metabolism, Gene Expression Regulation, Developmental, Zebrafish genetics, Zebrafish Proteins metabolism
- Abstract
Here, we report the identification and expression analysis of the zebrafish G protein gammaT1 subunit gene (gngT1) during development. Similar to its human and mouse homologs, we confirm zebrafish gngT1 is expressed in the developing retina, where its transcription overlaps with the photoreceptor cell-specific marker, rhodopsin (rho). Surprisingly, we also show zebrafish gngT1 is expressed in the dorsal diencephalon, where its transcription overlaps with the pineal specific markers, arylalkylamine N-acetyltransferase-2 (annat-2) and extra-ocular rhodopsin (exorh). Analysis of the proximal promoter sequence of the zebrafish gngT1 gene identifies several conserved binding sites for the cone-rod homeobox/orthodenticle (Crx/Otx) homeodomain family of transcription factors. Using a morpholino anti-sense approach in zebrafish, we show that targeted knockdown of otx5 potently suppresses gngT1 expression in the pineal gland, whereas knockdown of crx markedly reduces gngT1 expression in the retina. Taken together, these data indicate that pineal- and retinal-specific expression of the gngT1 gene are controlled by different transcription factors and exogenous signals.
- Published
- 2007
- Full Text
- View/download PDF
15. Zebrafish G protein gamma2 is required for VEGF signaling during angiogenesis.
- Author
-
Leung T, Chen H, Stauffer AM, Giger KE, Sinha S, Horstick EJ, Humbert JE, Hansen CA, and Robishaw JD
- Subjects
- Animals, GTP-Binding Protein gamma Subunits genetics, GTP-Binding Protein gamma Subunits physiology, GTP-Binding Proteins genetics, GTP-Binding Proteins physiology, Gene Expression Profiling, Models, Animal, Neovascularization, Physiologic physiology, Phenotype, Phospholipase C gamma metabolism, Protein Subunits genetics, Protein Subunits physiology, Proto-Oncogene Proteins c-akt metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Vascular Endothelial Growth Factor A physiology, Zebrafish, Zebrafish Proteins genetics, Zebrafish Proteins physiology, GTP-Binding Protein gamma Subunits pharmacology, GTP-Binding Proteins pharmacology, Neovascularization, Physiologic drug effects, Protein Subunits pharmacology, Signal Transduction drug effects, Vascular Endothelial Growth Factor A drug effects, Zebrafish Proteins pharmacology
- Abstract
Vascular endothelial growth factor (VEGF) is a major mediator of pathologic angiogenesis, a process necessary for the formation of new blood vessels to support tumor growth. Historically, VEGF has been thought to signal via receptor tyrosine kinases, which are not typically considered to be G protein dependent. Here, we show that targeted knockdown of the G protein gng2 gene (Ggamma2) blocks the normal angiogenic process in developing zebrafish embryos. Moreover, loss of gng2 function inhibits the ability of VEGF to promote the angiogenic sprouting of blood vessels by attenuating VEGF induced phosphorylation of phospholipase C-gamma1 (PLCgamma1) and serine/threonine kinase (AKT). Collectively, these results demonstrate a novel interaction between Ggamma2- and VEGF-dependent pathways to regulate the angiogenic process in a whole-animal model. Blocking VEGF function using a humanized anti-VEGF antibody has emerged as a promising treatment for colorectal, non-small lung cell, and breast cancers. However, this treatment may cause considerable side effects. Our findings provide a new opportunity for cotargeting G protein- and VEGF-dependent pathways to synergistically block pathologic angiogenesis, which may lead to a safer and more efficacious therapeutic regimen to fight cancer.
- Published
- 2006
- Full Text
- View/download PDF
16. Mice with deficiency of G protein gamma3 are lean and have seizures.
- Author
-
Schwindinger WF, Giger KE, Betz KS, Stauffer AM, Sunderlin EM, Sim-Selley LJ, Selley DE, Bronson SK, and Robishaw JD
- Subjects
- Adenylyl Cyclases metabolism, Adipose Tissue, Animals, Body Weight, Brain metabolism, Female, GTP-Binding Protein beta Subunits metabolism, Gene Targeting, Guanosine 5'-O-(3-Thiotriphosphate) metabolism, Heterotrimeric GTP-Binding Proteins genetics, Heterotrimeric GTP-Binding Proteins metabolism, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Seizures metabolism, Signal Transduction physiology, GTP-Binding Protein gamma Subunits genetics, GTP-Binding Protein gamma Subunits metabolism, Seizures genetics
- Abstract
Emerging evidence suggests that the gamma subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve gamma subtypes, gamma3 is abundantly and widely expressed in the brain. To identify specific functions and associations for gamma3, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3-/-). Confirming the efficacy and specificity of gene targeting, Gng3-/- mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for gamma3 in the brain, Gng3-/- mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for gamma3, these phenotypic changes are associated with significant reductions in beta2 and alphai3 subunit levels in certain regions of the brain. The finding that the Gng3-/- mice and the previously reported Gng7-/- mice display distinct phenotypes and different alphabetagamma subunit associations supports the notion that even closely related gamma subtypes, such as gamma3 and gamma7, perform unique functions in the context of the organism., (Copyright 2004 American Society for Microbiology)
- Published
- 2004
- Full Text
- View/download PDF
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