Regulation of postsynaptic gephyrin cluster size by protein phosphatase 1
The scaffolding protein gephyrin is essential for the clustering of glycine and GABAA receptors (GABAARs) at inhibitory synapses. Here, we provide evidence that the size of the postsynaptic gephyrin scaffold is controlled by dephosphorylation reactions. Treatment of cultured hippocampal neurons with...
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| Veröffentlicht in: | Molecular and cellular neuroscience 2010-07, Vol.44 (3), p.201-209 |
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| creator | Bausen, Melanie Weltzien, Felix Betz, Heinrich O'Sullivan, Gregory A. |
| description | The scaffolding protein gephyrin is essential for the clustering of glycine and GABAA receptors (GABAARs) at inhibitory synapses. Here, we provide evidence that the size of the postsynaptic gephyrin scaffold is controlled by dephosphorylation reactions. Treatment of cultured hippocampal neurons with the protein phosphatase inhibitors calyculin A and okadaic acid reduced the size of postsynaptic gephyrin clusters and increased cytoplasmic gephyrin staining. Protein phosphatase 1 (PP1) was found to colocalize with gephyrin at selected postsynaptic sites and to interact with gephyrin in transfected cells and brain extracts. Alanine or glutamate substitution of the two established serine/threonine phosphorylation sites in gephyrin failed to affect its clustering at inhibitory synapses and its ability to recruit γ2 subunit containing GABAARs. Our data are consistent with the postsynaptic gephyrin scaffold acting as a platform for PP1, which regulates gephyrin cluster size by dephosphorylation of gephyrin- or cytoskeleton-associated proteins. |
| doi_str_mv | 10.1016/j.mcn.2010.02.007 |
| format | Article |
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Here, we provide evidence that the size of the postsynaptic gephyrin scaffold is controlled by dephosphorylation reactions. Treatment of cultured hippocampal neurons with the protein phosphatase inhibitors calyculin A and okadaic acid reduced the size of postsynaptic gephyrin clusters and increased cytoplasmic gephyrin staining. Protein phosphatase 1 (PP1) was found to colocalize with gephyrin at selected postsynaptic sites and to interact with gephyrin in transfected cells and brain extracts. Alanine or glutamate substitution of the two established serine/threonine phosphorylation sites in gephyrin failed to affect its clustering at inhibitory synapses and its ability to recruit γ2 subunit containing GABAARs. 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Weltzien, Felix ; Betz, Heinrich ; O'Sullivan, Gregory A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-64feafcdad5510ba6cc0a34aba0803ddf9e2d80752ddc37db8764b2066075d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Alanine</topic><topic>Animals</topic><topic>Calyculin</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cells, Cultured</topic><topic>Cytoskeleton - metabolism</topic><topic>Cytoskeleton - ultrastructure</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>GABAA receptors</topic><topic>Gephyrin</topic><topic>Hippocampal neuron</topic><topic>Hippocampus - cytology</topic><topic>Humans</topic><topic>Inhibitory synapses</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - ultrastructure</topic><topic>Okadaic acid</topic><topic>Okadaic Acid - pharmacology</topic><topic>Oxazoles - pharmacology</topic><topic>Protein phosphatase</topic><topic>Protein Phosphatase 1 - antagonists & inhibitors</topic><topic>Protein Phosphatase 1 - metabolism</topic><topic>Rats</topic><topic>Receptors, GABA - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Synapses - drug effects</topic><topic>Synapses - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bausen, Melanie</creatorcontrib><creatorcontrib>Weltzien, Felix</creatorcontrib><creatorcontrib>Betz, Heinrich</creatorcontrib><creatorcontrib>O'Sullivan, Gregory A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Molecular and cellular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bausen, Melanie</au><au>Weltzien, Felix</au><au>Betz, Heinrich</au><au>O'Sullivan, Gregory A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of postsynaptic gephyrin cluster size by protein phosphatase 1</atitle><jtitle>Molecular and cellular neuroscience</jtitle><addtitle>Mol Cell Neurosci</addtitle><date>2010-07</date><risdate>2010</risdate><volume>44</volume><issue>3</issue><spage>201</spage><epage>209</epage><pages>201-209</pages><issn>1044-7431</issn><eissn>1095-9327</eissn><abstract>The scaffolding protein gephyrin is essential for the clustering of glycine and GABAA receptors (GABAARs) at inhibitory synapses. Here, we provide evidence that the size of the postsynaptic gephyrin scaffold is controlled by dephosphorylation reactions. Treatment of cultured hippocampal neurons with the protein phosphatase inhibitors calyculin A and okadaic acid reduced the size of postsynaptic gephyrin clusters and increased cytoplasmic gephyrin staining. Protein phosphatase 1 (PP1) was found to colocalize with gephyrin at selected postsynaptic sites and to interact with gephyrin in transfected cells and brain extracts. Alanine or glutamate substitution of the two established serine/threonine phosphorylation sites in gephyrin failed to affect its clustering at inhibitory synapses and its ability to recruit γ2 subunit containing GABAARs. Our data are consistent with the postsynaptic gephyrin scaffold acting as a platform for PP1, which regulates gephyrin cluster size by dephosphorylation of gephyrin- or cytoskeleton-associated proteins.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20206270</pmid><doi>10.1016/j.mcn.2010.02.007</doi><tpages>9</tpages></addata></record> |
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| subjects | Alanine Animals Calyculin Carrier Proteins - genetics Carrier Proteins - metabolism Cells, Cultured Cytoskeleton - metabolism Cytoskeleton - ultrastructure Enzyme Inhibitors - pharmacology GABAA receptors Gephyrin Hippocampal neuron Hippocampus - cytology Humans Inhibitory synapses Membrane Proteins - genetics Membrane Proteins - metabolism Neurons - drug effects Neurons - metabolism Neurons - ultrastructure Okadaic acid Okadaic Acid - pharmacology Oxazoles - pharmacology Protein phosphatase Protein Phosphatase 1 - antagonists & inhibitors Protein Phosphatase 1 - metabolism Rats Receptors, GABA - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Synapses - drug effects Synapses - metabolism |
| title | Regulation of postsynaptic gephyrin cluster size by protein phosphatase 1 |
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