PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction
Targeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2007-01, Vol.53 (2), p.201-215 |
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| creator | Zhang, Yali Guo, Huifu Kwan, Helen Wang, Ji-Wu Kosek, Jon Lu, Bingwei |
| description | Targeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell polarity regulator, is critically involved in controlling the postsynaptic localization of Dlg. PAR-1 is prominently localized at the
Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis. |
| doi_str_mv | 10.1016/j.neuron.2006.12.016 |
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Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2006.12.016</identifier><identifier>PMID: 17224403</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Animals, Genetically Modified ; Cell division ; CELLBIO ; Disease ; Drosophila ; Drosophila - physiology ; Drosophila Proteins - metabolism ; Drosophila Proteins - physiology ; Experiments ; Fluorescence Recovery After Photobleaching ; Glycogen Synthase Kinase 3 ; In Vitro Techniques ; Insects ; Kinases ; Mammals ; Microscopy ; Neurodegeneration ; Neuromuscular Junction - metabolism ; Neuromuscular Junction - physiology ; Neuromuscular Junction - ultrastructure ; Pathogenesis ; Phosphorylation ; Protein Kinases - metabolism ; Protein Kinases - physiology ; Protein-Serine-Threonine Kinases ; Proteins ; SIGNALING ; Synapses - physiology ; Synapses - ultrastructure ; Synaptic Transmission - physiology ; Tissue Distribution ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Neuron (Cambridge, Mass.), 2007-01, Vol.53 (2), p.201-215</ispartof><rights>2007 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Jan 18, 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-d27f577ac634257c185440015f24867667572e560c21bafb2e04f04dd34e6a943</citedby><cites>FETCH-LOGICAL-c520t-d27f577ac634257c185440015f24867667572e560c21bafb2e04f04dd34e6a943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuron.2006.12.016$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17224403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yali</creatorcontrib><creatorcontrib>Guo, Huifu</creatorcontrib><creatorcontrib>Kwan, Helen</creatorcontrib><creatorcontrib>Wang, Ji-Wu</creatorcontrib><creatorcontrib>Kosek, Jon</creatorcontrib><creatorcontrib>Lu, Bingwei</creatorcontrib><title>PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Targeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell polarity regulator, is critically involved in controlling the postsynaptic localization of Dlg. PAR-1 is prominently localized at the
Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis.</description><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Cell division</subject><subject>CELLBIO</subject><subject>Disease</subject><subject>Drosophila</subject><subject>Drosophila - physiology</subject><subject>Drosophila Proteins - metabolism</subject><subject>Drosophila Proteins - physiology</subject><subject>Experiments</subject><subject>Fluorescence Recovery After Photobleaching</subject><subject>Glycogen Synthase Kinase 3</subject><subject>In Vitro Techniques</subject><subject>Insects</subject><subject>Kinases</subject><subject>Mammals</subject><subject>Microscopy</subject><subject>Neurodegeneration</subject><subject>Neuromuscular Junction - metabolism</subject><subject>Neuromuscular Junction - physiology</subject><subject>Neuromuscular Junction - ultrastructure</subject><subject>Pathogenesis</subject><subject>Phosphorylation</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Kinases - physiology</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proteins</subject><subject>SIGNALING</subject><subject>Synapses - physiology</subject><subject>Synapses - ultrastructure</subject><subject>Synaptic Transmission - physiology</subject><subject>Tissue Distribution</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1vEzEUtBCIhsA_QMgSUm8bbK8_di9IVctHoYKoKmfL8b5NHG3sre2tlH-Po0QUOMDJ0njmvXkzCL2mZEEJle-2Cw9TDH7BCJELyhYFfIJmlLSq4rRtn6IZaVpZSabqM_QipS0hlIuWPkdnVDHGOaln6H55cVtR_NV5kwAvNyGNmxD3g8mQ8NWwxsZ3-BbW0xG5zgkvQ8pp782YncV3Jq4hO1-IGecN4KsYUhg3bjD428Hfbkq2iCP-MnmbXfAv0bPeDAlend45-vHxw93l5-rm-6fry4ubygpGctUx1QuljJU1Z0JZ2ojimFDRM95IJaUSioGQxDK6Mv2KAeE94V1Xc5Cm5fUcvT_OHafVDjoLPkcz6DG6nYl7HYzTf_54t9Hr8KDLpuKAlgHnpwEx3E-Qst65ZGEYjIcwJS2bljHJmv8SGVEtl4IV4tu_iNswRV9S0FSQWspalLLmiB9ZtkSZIvS_PFOiD9XrrT5Wrw_Va8p0AYvsze_3PopOXT8GAiX1BwdRJ-vAW-hcBJt1F9y_N_wEKCnCQQ</recordid><startdate>20070118</startdate><enddate>20070118</enddate><creator>Zhang, Yali</creator><creator>Guo, Huifu</creator><creator>Kwan, Helen</creator><creator>Wang, Ji-Wu</creator><creator>Kosek, Jon</creator><creator>Lu, Bingwei</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7SS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070118</creationdate><title>PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction</title><author>Zhang, Yali ; Guo, Huifu ; Kwan, Helen ; Wang, Ji-Wu ; Kosek, Jon ; Lu, Bingwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-d27f577ac634257c185440015f24867667572e560c21bafb2e04f04dd34e6a943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Cell division</topic><topic>CELLBIO</topic><topic>Disease</topic><topic>Drosophila</topic><topic>Drosophila - physiology</topic><topic>Drosophila Proteins - metabolism</topic><topic>Drosophila Proteins - physiology</topic><topic>Experiments</topic><topic>Fluorescence Recovery After Photobleaching</topic><topic>Glycogen Synthase Kinase 3</topic><topic>In Vitro Techniques</topic><topic>Insects</topic><topic>Kinases</topic><topic>Mammals</topic><topic>Microscopy</topic><topic>Neurodegeneration</topic><topic>Neuromuscular Junction - metabolism</topic><topic>Neuromuscular Junction - physiology</topic><topic>Neuromuscular Junction - ultrastructure</topic><topic>Pathogenesis</topic><topic>Phosphorylation</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Kinases - physiology</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Proteins</topic><topic>SIGNALING</topic><topic>Synapses - physiology</topic><topic>Synapses - ultrastructure</topic><topic>Synaptic Transmission - physiology</topic><topic>Tissue Distribution</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yali</creatorcontrib><creatorcontrib>Guo, Huifu</creatorcontrib><creatorcontrib>Kwan, Helen</creatorcontrib><creatorcontrib>Wang, Ji-Wu</creatorcontrib><creatorcontrib>Kosek, Jon</creatorcontrib><creatorcontrib>Lu, Bingwei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yali</au><au>Guo, Huifu</au><au>Kwan, Helen</au><au>Wang, Ji-Wu</au><au>Kosek, Jon</au><au>Lu, Bingwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2007-01-18</date><risdate>2007</risdate><volume>53</volume><issue>2</issue><spage>201</spage><epage>215</epage><pages>201-215</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>Targeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell polarity regulator, is critically involved in controlling the postsynaptic localization of Dlg. PAR-1 is prominently localized at the
Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17224403</pmid><doi>10.1016/j.neuron.2006.12.016</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Genetically Modified Cell division CELLBIO Disease Drosophila Drosophila - physiology Drosophila Proteins - metabolism Drosophila Proteins - physiology Experiments Fluorescence Recovery After Photobleaching Glycogen Synthase Kinase 3 In Vitro Techniques Insects Kinases Mammals Microscopy Neurodegeneration Neuromuscular Junction - metabolism Neuromuscular Junction - physiology Neuromuscular Junction - ultrastructure Pathogenesis Phosphorylation Protein Kinases - metabolism Protein Kinases - physiology Protein-Serine-Threonine Kinases Proteins SIGNALING Synapses - physiology Synapses - ultrastructure Synaptic Transmission - physiology Tissue Distribution Tumor Suppressor Proteins - metabolism |
| title | PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction |
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