SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b

The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, su...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochemical journal 2011-04, Vol.435 (2), p.365-371
Hauptverfasser: Dütting, Eva, Schröder-Kress, Nadja, Sticht, Heinrich, Enz, Ralf
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 371
container_issue 2
container_start_page 365
container_title Biochemical journal
container_volume 435
creator Dütting, Eva
Schröder-Kress, Nadja
Sticht, Heinrich
Enz, Ralf
description The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, such as phosphorylation and SUMOylation (SUMO is small ubiquitin-related modifier). In the present study, we searched for proteins interacting with the intracellular C-termini of the metabotropic glutamate receptors mGluR8a and mGluR8b and identified proteins of the SUMOylation and NEDDylation machinery. The SUMO E3 ligases Pias1 [Pias is protein inhibitor of activated STAT (signal transducer and activator of transcription)] and Pias3L interacted strongly with mGluR8b, and were co-localized with the E2-conjugating Ubc9, SUMO1 and mGluR8b in cell bodies present in the ganglion cell layer of the mammalian retina. SUMO1 conjugation of Lys882, present in a bona fide consensus sequence for SUMOylation (VKSE) in the mGluR8b C-terminus, was enhanced by addition of Pias1, consistent with an interaction between both proteins. Mutation of Lys882 to arginine reduced, but did not abolish, mGluR8b SUMOylation. Co-mutating a second lysine residue (Lys903) located in the mGluR8b isoform-specific C-terminus largely prevented SUMO1 conjugation by Ubc9. Modelling studies suggested that Lys903 contacts Ubc9 and thus is part of the non-canonical SUMOylation site VKSG. In summary, the results of the present study show in vivo SUMOylation of the complete mGluR8b and co-localize proteins of the SUMOylation machinery in the retina.
doi_str_mv 10.1042/BJ20101854
format Article
fullrecord <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_00581537v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>875072420</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-3ee797a7c6c3de8067cae4a5ba6adf890472311ab789ebedfa7c7a2289e124043</originalsourceid><addsrcrecordid>eNpF0UtPhDAQB_DGaHR9XPwApjejCTothXaPanxmzR50z2SAYcUAxbYY_fayro9Tp82v_2RmGDsUcCZAyfPLBwkChEnUBpsIpSEyWppNNgGZqigFKXbYrvevAEKBgm22I4U0RoKcsO5p8Tjn1zFv6iV68hwdcfroHXlPJa87Hl6IOwp1hxy7ciyXQ4OB-Orj51jVtuO2-mYtBcxtcLavC75shoDtSjoqqA_WcZPvs60KG08HP-ceW9xcP1_dRbP57f3VxSwq4iQNUUykpxp1kRZxSQZSXSApTHJMsazMFJSWsRCYazOlnMpqpBqlHG9Cjj3Ge-xknfuCTda7ukX3mVmss7uLWbZ6A0iMSGL9LkZ7vLa9s28D-ZC1tS-oabAjO_jM6AS0VBJGebqWhbPeO6r-ogVkq1Vk_6sY8dFP7JC3VP7R39nHX12pgpo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>875072420</pqid></control><display><type>article</type><title>SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b</title><source>MEDLINE</source><source>NCBI_PubMed Central(免费)</source><source>EZB*</source><creator>Dütting, Eva ; Schröder-Kress, Nadja ; Sticht, Heinrich ; Enz, Ralf</creator><creatorcontrib>Dütting, Eva ; Schröder-Kress, Nadja ; Sticht, Heinrich ; Enz, Ralf</creatorcontrib><description>The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, such as phosphorylation and SUMOylation (SUMO is small ubiquitin-related modifier). In the present study, we searched for proteins interacting with the intracellular C-termini of the metabotropic glutamate receptors mGluR8a and mGluR8b and identified proteins of the SUMOylation and NEDDylation machinery. The SUMO E3 ligases Pias1 [Pias is protein inhibitor of activated STAT (signal transducer and activator of transcription)] and Pias3L interacted strongly with mGluR8b, and were co-localized with the E2-conjugating Ubc9, SUMO1 and mGluR8b in cell bodies present in the ganglion cell layer of the mammalian retina. SUMO1 conjugation of Lys882, present in a bona fide consensus sequence for SUMOylation (VKSE) in the mGluR8b C-terminus, was enhanced by addition of Pias1, consistent with an interaction between both proteins. Mutation of Lys882 to arginine reduced, but did not abolish, mGluR8b SUMOylation. Co-mutating a second lysine residue (Lys903) located in the mGluR8b isoform-specific C-terminus largely prevented SUMO1 conjugation by Ubc9. Modelling studies suggested that Lys903 contacts Ubc9 and thus is part of the non-canonical SUMOylation site VKSG. In summary, the results of the present study show in vivo SUMOylation of the complete mGluR8b and co-localize proteins of the SUMOylation machinery in the retina.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/BJ20101854</identifier><identifier>PMID: 21288202</identifier><language>eng</language><publisher>England: Portland Press</publisher><subject>Amino Acid Sequence ; Animals ; Catalytic Domain - genetics ; Cells, Cultured ; Gene Expression Regulation, Enzymologic ; Humans ; Mice ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Protein Inhibitors of Activated STAT - genetics ; Protein Inhibitors of Activated STAT - metabolism ; Protein Inhibitors of Activated STAT - physiology ; Protein Interaction Domains and Motifs - genetics ; Protein Isoforms - metabolism ; Protein Processing, Post-Translational - genetics ; Protein Structure, Quaternary ; Rats ; Receptors, Metabotropic Glutamate - chemistry ; Receptors, Metabotropic Glutamate - genetics ; Receptors, Metabotropic Glutamate - metabolism ; Retina - enzymology ; Retina - metabolism ; SUMO-1 Protein - chemistry ; SUMO-1 Protein - genetics ; SUMO-1 Protein - metabolism ; Sumoylation - genetics ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism</subject><ispartof>Biochemical journal, 2011-04, Vol.435 (2), p.365-371</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-3ee797a7c6c3de8067cae4a5ba6adf890472311ab789ebedfa7c7a2289e124043</citedby><cites>FETCH-LOGICAL-c356t-3ee797a7c6c3de8067cae4a5ba6adf890472311ab789ebedfa7c7a2289e124043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21288202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00581537$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Dütting, Eva</creatorcontrib><creatorcontrib>Schröder-Kress, Nadja</creatorcontrib><creatorcontrib>Sticht, Heinrich</creatorcontrib><creatorcontrib>Enz, Ralf</creatorcontrib><title>SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, such as phosphorylation and SUMOylation (SUMO is small ubiquitin-related modifier). In the present study, we searched for proteins interacting with the intracellular C-termini of the metabotropic glutamate receptors mGluR8a and mGluR8b and identified proteins of the SUMOylation and NEDDylation machinery. The SUMO E3 ligases Pias1 [Pias is protein inhibitor of activated STAT (signal transducer and activator of transcription)] and Pias3L interacted strongly with mGluR8b, and were co-localized with the E2-conjugating Ubc9, SUMO1 and mGluR8b in cell bodies present in the ganglion cell layer of the mammalian retina. SUMO1 conjugation of Lys882, present in a bona fide consensus sequence for SUMOylation (VKSE) in the mGluR8b C-terminus, was enhanced by addition of Pias1, consistent with an interaction between both proteins. Mutation of Lys882 to arginine reduced, but did not abolish, mGluR8b SUMOylation. Co-mutating a second lysine residue (Lys903) located in the mGluR8b isoform-specific C-terminus largely prevented SUMO1 conjugation by Ubc9. Modelling studies suggested that Lys903 contacts Ubc9 and thus is part of the non-canonical SUMOylation site VKSG. In summary, the results of the present study show in vivo SUMOylation of the complete mGluR8b and co-localize proteins of the SUMOylation machinery in the retina.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Catalytic Domain - genetics</subject><subject>Cells, Cultured</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Protein Inhibitors of Activated STAT - genetics</subject><subject>Protein Inhibitors of Activated STAT - metabolism</subject><subject>Protein Inhibitors of Activated STAT - physiology</subject><subject>Protein Interaction Domains and Motifs - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Processing, Post-Translational - genetics</subject><subject>Protein Structure, Quaternary</subject><subject>Rats</subject><subject>Receptors, Metabotropic Glutamate - chemistry</subject><subject>Receptors, Metabotropic Glutamate - genetics</subject><subject>Receptors, Metabotropic Glutamate - metabolism</subject><subject>Retina - enzymology</subject><subject>Retina - metabolism</subject><subject>SUMO-1 Protein - chemistry</subject><subject>SUMO-1 Protein - genetics</subject><subject>SUMO-1 Protein - metabolism</subject><subject>Sumoylation - genetics</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0UtPhDAQB_DGaHR9XPwApjejCTothXaPanxmzR50z2SAYcUAxbYY_fayro9Tp82v_2RmGDsUcCZAyfPLBwkChEnUBpsIpSEyWppNNgGZqigFKXbYrvevAEKBgm22I4U0RoKcsO5p8Tjn1zFv6iV68hwdcfroHXlPJa87Hl6IOwp1hxy7ciyXQ4OB-Orj51jVtuO2-mYtBcxtcLavC75shoDtSjoqqA_WcZPvs60KG08HP-ceW9xcP1_dRbP57f3VxSwq4iQNUUykpxp1kRZxSQZSXSApTHJMsazMFJSWsRCYazOlnMpqpBqlHG9Cjj3Ge-xknfuCTda7ukX3mVmss7uLWbZ6A0iMSGL9LkZ7vLa9s28D-ZC1tS-oabAjO_jM6AS0VBJGebqWhbPeO6r-ogVkq1Vk_6sY8dFP7JC3VP7R39nHX12pgpo</recordid><startdate>20110415</startdate><enddate>20110415</enddate><creator>Dütting, Eva</creator><creator>Schröder-Kress, Nadja</creator><creator>Sticht, Heinrich</creator><creator>Enz, Ralf</creator><general>Portland Press</general><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>7X8</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20110415</creationdate><title>SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b</title><author>Dütting, Eva ; Schröder-Kress, Nadja ; Sticht, Heinrich ; Enz, Ralf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-3ee797a7c6c3de8067cae4a5ba6adf890472311ab789ebedfa7c7a2289e124043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Catalytic Domain - genetics</topic><topic>Cells, Cultured</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Humans</topic><topic>Mice</topic><topic>Models, Biological</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Protein Inhibitors of Activated STAT - genetics</topic><topic>Protein Inhibitors of Activated STAT - metabolism</topic><topic>Protein Inhibitors of Activated STAT - physiology</topic><topic>Protein Interaction Domains and Motifs - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Processing, Post-Translational - genetics</topic><topic>Protein Structure, Quaternary</topic><topic>Rats</topic><topic>Receptors, Metabotropic Glutamate - chemistry</topic><topic>Receptors, Metabotropic Glutamate - genetics</topic><topic>Receptors, Metabotropic Glutamate - metabolism</topic><topic>Retina - enzymology</topic><topic>Retina - metabolism</topic><topic>SUMO-1 Protein - chemistry</topic><topic>SUMO-1 Protein - genetics</topic><topic>SUMO-1 Protein - metabolism</topic><topic>Sumoylation - genetics</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dütting, Eva</creatorcontrib><creatorcontrib>Schröder-Kress, Nadja</creatorcontrib><creatorcontrib>Sticht, Heinrich</creatorcontrib><creatorcontrib>Enz, Ralf</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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dütting, Eva</au><au>Schröder-Kress, Nadja</au><au>Sticht, Heinrich</au><au>Enz, Ralf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>2011-04-15</date><risdate>2011</risdate><volume>435</volume><issue>2</issue><spage>365</spage><epage>371</epage><pages>365-371</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, such as phosphorylation and SUMOylation (SUMO is small ubiquitin-related modifier). In the present study, we searched for proteins interacting with the intracellular C-termini of the metabotropic glutamate receptors mGluR8a and mGluR8b and identified proteins of the SUMOylation and NEDDylation machinery. The SUMO E3 ligases Pias1 [Pias is protein inhibitor of activated STAT (signal transducer and activator of transcription)] and Pias3L interacted strongly with mGluR8b, and were co-localized with the E2-conjugating Ubc9, SUMO1 and mGluR8b in cell bodies present in the ganglion cell layer of the mammalian retina. SUMO1 conjugation of Lys882, present in a bona fide consensus sequence for SUMOylation (VKSE) in the mGluR8b C-terminus, was enhanced by addition of Pias1, consistent with an interaction between both proteins. Mutation of Lys882 to arginine reduced, but did not abolish, mGluR8b SUMOylation. Co-mutating a second lysine residue (Lys903) located in the mGluR8b isoform-specific C-terminus largely prevented SUMO1 conjugation by Ubc9. Modelling studies suggested that Lys903 contacts Ubc9 and thus is part of the non-canonical SUMOylation site VKSG. In summary, the results of the present study show in vivo SUMOylation of the complete mGluR8b and co-localize proteins of the SUMOylation machinery in the retina.</abstract><cop>England</cop><pub>Portland Press</pub><pmid>21288202</pmid><doi>10.1042/BJ20101854</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0264-6021
ispartof Biochemical journal, 2011-04, Vol.435 (2), p.365-371
issn 0264-6021
1470-8728
language eng
recordid cdi_hal_primary_oai_HAL_hal_00581537v1
source MEDLINE; NCBI_PubMed Central(免费); EZB*
subjects Amino Acid Sequence
Animals
Catalytic Domain - genetics
Cells, Cultured
Gene Expression Regulation, Enzymologic
Humans
Mice
Models, Biological
Models, Molecular
Molecular Sequence Data
Protein Inhibitors of Activated STAT - genetics
Protein Inhibitors of Activated STAT - metabolism
Protein Inhibitors of Activated STAT - physiology
Protein Interaction Domains and Motifs - genetics
Protein Isoforms - metabolism
Protein Processing, Post-Translational - genetics
Protein Structure, Quaternary
Rats
Receptors, Metabotropic Glutamate - chemistry
Receptors, Metabotropic Glutamate - genetics
Receptors, Metabotropic Glutamate - metabolism
Retina - enzymology
Retina - metabolism
SUMO-1 Protein - chemistry
SUMO-1 Protein - genetics
SUMO-1 Protein - metabolism
Sumoylation - genetics
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
title SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T02%3A46%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SUMO%20E3%20ligases%20are%20expressed%20in%20the%20retina%20and%20regulate%20SUMOylation%20of%20the%20metabotropic%20glutamate%20receptor%208b&rft.jtitle=Biochemical%20journal&rft.au=D%C3%BCtting,%20Eva&rft.date=2011-04-15&rft.volume=435&rft.issue=2&rft.spage=365&rft.epage=371&rft.pages=365-371&rft.issn=0264-6021&rft.eissn=1470-8728&rft_id=info:doi/10.1042/BJ20101854&rft_dat=%3Cproquest_hal_p%3E875072420%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=875072420&rft_id=info:pmid/21288202&rfr_iscdi=true