The Golgi-Associated PDZ Domain Protein Gopc/PIST Is Required for Synaptic Targeting of mGluR5
Copyright policy )The Golgi-Associated PDZ Domain Protein Gopc/PIST Is Required for Synaptic Targeting of mGluR5
AbstractIn neuronal cells, many membrane receptors interact via their intracellular, C-terminal tails with PSD-95/discs large/ZO-1 (PDZ) domain proteins. Some PDZ proteins act as scaffold proteins. In addition, there are a few PDZ proteins such as Gopc which bind to receptors during intracellular transport. Gopc is localized at the trans-Golgi network (TGN) and binds to a variety of receptors, many of which are eventually targeted to postsynaptic sites. We have analyzed the role of Gopc by knockdown in primary cultured neurons and by generating a conditional Gopc knockout (KO) mouse line. In neurons, targeting of neuroligin 1 (Nlgn1) and metabotropic glutamate receptor 5 (mGlu5) to the plasma membrane was impaired upon depletion of Gopc, whereas NMDA receptors were not affected. In the hippocampus and cortex of Gopc KO animals, expression levels of Gopc-associated receptors were not altered, while their subcellular localization was disturbed. The targeting of mGlu5 to the postsynaptic density was reduced, coinciding with alterations in mGluR-dependent synaptic plasticity and deficiencies in a contextual fear conditioning paradigm. Our data imply Gopc in the correct subcellular sorting of its associated mGlu5 receptor in vivo.
- Center for Behavioral Brain Sciences Germany
- Universität Hamburg Germany
- Institut für Humangenetik Germany
- German Center for Neurodegenerative Diseases Germany
- Otto-von-Guericke-University Germany
Male, physiology [Golgi Matrix Proteins], Neuroligin, Cell Adhesion Molecules, Neuronal, PDZ domain, Conditioning, Classical, Primary Cell Culture, Cerebral Cortex/cytology [MeSH] ; Morris Water Maze Test [MeSH] ; Conditioning, Classical [MeSH] ; Post-Synaptic Density/metabolism [MeSH] ; mGlu5 ; Trans-Golgi network ; Original Article ; Long-term depression ; Protein Transport/physiology [MeSH] ; Carrier Proteins/antagonists ; Cell Adhesion Molecules, Neuronal/metabolism [MeSH] ; Male [MeSH] ; Carrier Proteins/genetics [MeSH] ; Gene Expression Regulation [MeSH] ; Neuroligin ; Primary Cell Culture [MeSH] ; Adaptor Proteins, Signal Transducing/physiology [MeSH] ; Female [MeSH] ; RNA, Small Interfering/pharmacology [MeSH] ; Open Field Test [MeSH] ; Golgi Matrix Proteins/physiology [MeSH] ; Rats [MeSH] ; Receptor, Metabotropic Glutamate 5/metabolism [MeSH] ; Animals [MeSH] ; Mice, Knockout [MeSH] ; Synaptic Membranes/metabolism [MeSH] ; Carrier Proteins/physiology [MeSH] ; Mice [MeSH] ; Subcellular Fractions/metabolism [MeSH] ; Adaptor Proteins, Signal Transducing/deficiency [MeSH] ; Cells, Cultured [MeSH] ; Hippocampus/cytology [MeSH] ; PDZ domain ; Fear/physiology [MeSH] ; Golgi Matrix Proteins/deficiency [MeSH], genetics [Carrier Proteins], Hippocampus, cytology [Cerebral Cortex], Mice, deficiency [Adaptor Proteins, Signal Transducing], physiology [Carrier Proteins], metabolism [Cell Adhesion Molecules, Neuronal], Morris Water Maze Test, Animals, Cells, Cultured, Adaptor Proteins, Signal Transducing, Cerebral Cortex, Mice, Knockout, Long-term depression, deficiency [Golgi Matrix Proteins], pharmacology [RNA, Small Interfering], Golgi Matrix Proteins, Post-Synaptic Density, Fear, Rats, metabolism [Subcellular Fractions], Protein Transport, Trans-Golgi network, metabolism [Post-Synaptic Density], Gene Expression Regulation, cytology [Hippocampus], antagonists & inhibitors [Carrier Proteins], physiology [Protein Transport], metabolism [Synaptic Membranes], mGlu5, Original Article, Female, physiology [Adaptor Proteins, Signal Transducing], Carrier Proteins, metabolism [Receptor, Metabotropic Glutamate 5], Open Field Test, physiology [Fear], ddc: ddc:570
Male, physiology [Golgi Matrix Proteins], Neuroligin, Cell Adhesion Molecules, Neuronal, PDZ domain, Conditioning, Classical, Primary Cell Culture, Cerebral Cortex/cytology [MeSH] ; Morris Water Maze Test [MeSH] ; Conditioning, Classical [MeSH] ; Post-Synaptic Density/metabolism [MeSH] ; mGlu5 ; Trans-Golgi network ; Original Article ; Long-term depression ; Protein Transport/physiology [MeSH] ; Carrier Proteins/antagonists ; Cell Adhesion Molecules, Neuronal/metabolism [MeSH] ; Male [MeSH] ; Carrier Proteins/genetics [MeSH] ; Gene Expression Regulation [MeSH] ; Neuroligin ; Primary Cell Culture [MeSH] ; Adaptor Proteins, Signal Transducing/physiology [MeSH] ; Female [MeSH] ; RNA, Small Interfering/pharmacology [MeSH] ; Open Field Test [MeSH] ; Golgi Matrix Proteins/physiology [MeSH] ; Rats [MeSH] ; Receptor, Metabotropic Glutamate 5/metabolism [MeSH] ; Animals [MeSH] ; Mice, Knockout [MeSH] ; Synaptic Membranes/metabolism [MeSH] ; Carrier Proteins/physiology [MeSH] ; Mice [MeSH] ; Subcellular Fractions/metabolism [MeSH] ; Adaptor Proteins, Signal Transducing/deficiency [MeSH] ; Cells, Cultured [MeSH] ; Hippocampus/cytology [MeSH] ; PDZ domain ; Fear/physiology [MeSH] ; Golgi Matrix Proteins/deficiency [MeSH], genetics [Carrier Proteins], Hippocampus, cytology [Cerebral Cortex], Mice, deficiency [Adaptor Proteins, Signal Transducing], physiology [Carrier Proteins], metabolism [Cell Adhesion Molecules, Neuronal], Morris Water Maze Test, Animals, Cells, Cultured, Adaptor Proteins, Signal Transducing, Cerebral Cortex, Mice, Knockout, Long-term depression, deficiency [Golgi Matrix Proteins], pharmacology [RNA, Small Interfering], Golgi Matrix Proteins, Post-Synaptic Density, Fear, Rats, metabolism [Subcellular Fractions], Protein Transport, Trans-Golgi network, metabolism [Post-Synaptic Density], Gene Expression Regulation, cytology [Hippocampus], antagonists & inhibitors [Carrier Proteins], physiology [Protein Transport], metabolism [Synaptic Membranes], mGlu5, Original Article, Female, physiology [Adaptor Proteins, Signal Transducing], Carrier Proteins, metabolism [Receptor, Metabotropic Glutamate 5], Open Field Test, physiology [Fear], ddc: ddc:570
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