Biomaterial Database

Gravin orchestrates protein kinase A and β2-adrenergic receptor signaling critical for synaptic plasticity and memory. 2012

Robbert Havekes, and David A Canton, and Alan J Park, and Ted Huang, and Ting Nie, and Jonathan P Day, and Leonardo A Guercio, and Quinn Grimes, and Vincent Luczak, and Irwin H Gelman, and George S Baillie, and John D Scott, and Ted Abel

Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018, USA. havekesr@sas.upenn.edu

A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plasticity and memory storage. In the forebrain, the anchoring protein gravin recruits a signaling complex containing PKA, PKC, calmodulin, and PDE4D (phosphodiesterase 4D) to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including β2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal β2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK in the CA1 region of the hippocampus are attenuated in mice lacking gravin-α. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced β2-adrenergic receptor signaling and ERK activation in the hippocampus in vivo, thereby organizing molecular interactions between glutamatergic and noradrenergic signaling pathways for long-lasting synaptic plasticity, and memory storage.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297	Male		Males
D008568	Memory	Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D009473	Neuronal Plasticity	The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.	Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260	Female		Females
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia