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Your search keyword '"Kenneth H. Moberg"' showing total 4 results
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4 results on '"Kenneth H. Moberg"'

1. The Conserved, Disease-Associated RNA Binding Protein dNab2 Interacts with the Fragile X Protein Ortholog in Drosophila Neurons

Author

Rick S. Bienkowski, Ayan Banerjee, J. Christopher Rounds, Jennifer Rha, Omotola F. Omotade, Christina Gross, Kevin J. Morris, Sara W. Leung, ChangHui Pak, Stephanie K. Jones, Michael R. Santoro, Stephen T. Warren, James Q. Zheng, Gary J. Bassell, Anita H. Corbett, and Kenneth H. Moberg

Subjects
dNab2, fragile X mental retardation protein, RNA binding protein, poly(A) tail, CamKII, futsch, Drosophila, neurodevelopment, memory, ZC3H14, Biology (General), QH301-705.5
Abstract

The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII, but not futsch, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A) tail length, similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. Altogether, these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14.

Published
2017
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2. Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome

Author

Christina Gross, Chia-Wei Chang, Seth M. Kelly, Aditi Bhattacharya, Sean M.J. McBride, Scott W. Danielson, Michael Q. Jiang, Chi Bun Chan, Keqiang Ye, Jay R. Gibson, Eric Klann, Thomas A. Jongens, Kenneth H. Moberg, Kimberly M. Huber, and Gary J. Bassell

Subjects
Biology (General), QH301-705.5
Abstract

The PI3K enhancer PIKE links PI3K catalytic subunits to group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS). Normalizing elevated PIKE protein levels in FXS mice reversed deficits in molecular and cellular plasticity and improved behavior. Notably, PIKE reduction rescued PI3K-dependent and -independent neuronal defects in FXS. We further show that PI3K signaling is increased in a fly model of FXS and that genetic reduction of the Drosophila ortholog of PIKE, CenG1A rescued excessive PI3K signaling, mushroom body defects, and impaired short-term memory in these flies. Our results demonstrate a crucial role of increased PIKE expression in exaggerated mGlu1/5 signaling causing neuronal defects in FXS.

Published
2015
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3. Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome

Author

Chia Wei Chang, Thomas A. Jongens, Sean M.J. McBride, Keqiang Ye, Aditi Bhattacharya, Kenneth H. Moberg, Eric Klann, Chi Bun Chan, Michael Q. Jiang, Gary J. Bassell, Scott Walter Danielson, Jay R. Gibson, Kimberly M. Huber, Christina Gross, and Seth M. Kelly

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Dendritic spine, GTPase-activating protein, Dendritic Spines, Receptor, Metabotropic Glutamate 5, Nerve Tissue Proteins, Biology, Receptors, Metabotropic Glutamate, General Biochemistry, Genetics and Molecular Biology, Article, GTP Phosphohydrolases, Fragile X Mental Retardation Protein, Mice, Phosphatidylinositol 3-Kinases, Neuroplasticity, medicine, Animals, Drosophila Proteins, lcsh:QH301-705.5, Mushroom Bodies, Genetics, Mice, Knockout, Neuronal Plasticity, Behavior, Animal, fungi, GTPase-Activating Proteins, Brain, medicine.disease, Fragile X syndrome, Disease Models, Animal, Gene Expression Regulation, lcsh:Biology (General), Metabotropic glutamate receptor, Fragile X Syndrome, Protein Biosynthesis, Synaptic plasticity, Mushroom bodies, Drosophila, Signal transduction, Neuroscience, Signal Transduction
Abstract

SummaryThe PI3K enhancer PIKE links PI3K catalytic subunits to group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS). Normalizing elevated PIKE protein levels in FXS mice reversed deficits in molecular and cellular plasticity and improved behavior. Notably, PIKE reduction rescued PI3K-dependent and -independent neuronal defects in FXS. We further show that PI3K signaling is increased in a fly model of FXS and that genetic reduction of the Drosophila ortholog of PIKE, CenG1A rescued excessive PI3K signaling, mushroom body defects, and impaired short-term memory in these flies. Our results demonstrate a crucial role of increased PIKE expression in exaggerated mGlu1/5 signaling causing neuronal defects in FXS.

Published
2015

4. The Conserved, Disease-Associated RNA Binding Protein dNab2 Interacts with the Fragile X Protein Ortholog in Drosophila Neurons

Author

Gary J. Bassell, Rick Bienkowski, Ayan Banerjee, Stephen T. Warren, Kenneth H. Moberg, Michael R. Santoro, James Q. Zheng, Omotola F. Omotade, Stephanie K. Jones, Anita H. Corbett, Christina Gross, Kevin J. Morris, ChangHui Pak, Jennifer Rha, Sara W. Leung, and J. Christopher Rounds

Subjects
0301 basic medicine, Male, Polyadenylation, RNA-binding protein, poly(A) tail, dNab2, Biology, General Biochemistry, Genetics and Molecular Biology, Article, CamKII, 03 medical and health sciences, Fragile X Mental Retardation Protein, Mice, 0302 clinical medicine, Memory, Ca2+/calmodulin-dependent protein kinase, Cell Line, Tumor, medicine, Animals, Drosophila Proteins, Gene Regulatory Networks, RNA, Messenger, Axon, lcsh:QH301-705.5, Cells, Cultured, Genetics, Regulation of gene expression, Neurons, Messenger RNA, neurodevelopment, RNA, Gene Expression Regulation, Developmental, RNA-Binding Proteins, RNA binding protein, futsch, Smell, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), nervous system, ZC3H14, Drosophila, Female, Calcium-Calmodulin-Dependent Protein Kinase Type 2, 030217 neurology & neurosurgery, Drosophila Protein
Abstract

The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII, but not futsch, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A) tail length, similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. Altogether, these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14.

Published
2016

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