MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens
The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening met...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-06, Vol.8 (6), p.e67608 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 6 |
| container_start_page | e67608 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Petko, Jessica Justice-Bitner, Stephanie Jin, Jay Wong, Victoria Kittanakom, Saranya Ferraro, Thomas N Stagljar, Igor Levenson, Robert |
| description | The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening methods to identify a cohort of novel MOR interacting proteins (MORIPs). The interaction between the MOR and a subset of MORIPs was validated in pulldown, co-immunoprecipitation, and co-localization studies using HEK293 cells stably expressing the MOR as well as rodent brain. Additionally, a subset of MORIPs was found capable of interaction with the delta and kappa opioid receptors, suggesting that they may represent general opioid receptor interacting proteins (ORIPS). Expression of several MORIPs was altered in specific mouse brain regions after chronic treatment with morphine, suggesting that these proteins may play a role in response to opioid agonist drugs. Based on the known function of these newly identified MORIPs, the interactions forming the MOR signalplex are hypothesized to be important for MOR signaling and intracellular trafficking. Understanding the molecular complexity of MOR/MORIP interactions provides a conceptual framework for defining the cellular mechanisms of MOR signaling in brain and may be critical for determining the physiological basis of opioid tolerance and addiction. |
| doi_str_mv | 10.1371/journal.pone.0067608 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1372350743</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_f4e918128ad248b9b2701d7330a12b3a</doaj_id><sourcerecordid>3007994371</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-cd4aeb8066ce64bbb25a829b99dcf48be8201f6c04dd8fb6a3f09c32dbcd8a903</originalsourceid><addsrcrecordid>eNp1kttuEzEQhlcIREvhDRBY4nqDDxuvzQVSVVGoVFQJwbXlw2ziaGMvtrcoz8EL1yFp1V5w5fHMP9-Mfk3TvCV4QVhPPm7inIIeF1MMsMCY9xyLZ80pkYy2nGL2_FF80rzKeYPxkgnOXzYnlIkO9508bf5-v_mBfEYhFgQhzqv1J-QdhOIHb3XxMaA41OotjGg7t3Hy0TuUwMJUYkI-FEjaFh9WaEqxgA8ZzXn_LUk7vwfoEeng0Da6yoQawNYkHQDtQOeCyp_YrncmVWy2CSDk182LQY8Z3hzfs-bX5ZefF9_a65uvVxfn161dUl5a6zoNRmDOLfDOGEOXWlBppHR26IQBQTEZuMWdc2IwXLMBS8uoM9YJLTE7a94fuNMYszr6mVV1l7JltYdVxdVB4aLeqCn5rU47FbVX_xIxrZROxdsR1NCBJIJQoR2tw6WhPSauZwxrQg3TlfX5OG02W3C2epz0-AT6tBL8Wq3irWJcLiWmFfDhCEjx9wy5_Gfl7qCyKeacYHiYQPBeR-671P5w1PFwatu7x9s9NN1fCrsDFVrGVA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1372350743</pqid></control><display><type>article</type><title>MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Petko, Jessica ; Justice-Bitner, Stephanie ; Jin, Jay ; Wong, Victoria ; Kittanakom, Saranya ; Ferraro, Thomas N ; Stagljar, Igor ; Levenson, Robert</creator><contributor>Harvey, Brandon K.</contributor><creatorcontrib>Petko, Jessica ; Justice-Bitner, Stephanie ; Jin, Jay ; Wong, Victoria ; Kittanakom, Saranya ; Ferraro, Thomas N ; Stagljar, Igor ; Levenson, Robert ; Harvey, Brandon K.</creatorcontrib><description>The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening methods to identify a cohort of novel MOR interacting proteins (MORIPs). The interaction between the MOR and a subset of MORIPs was validated in pulldown, co-immunoprecipitation, and co-localization studies using HEK293 cells stably expressing the MOR as well as rodent brain. Additionally, a subset of MORIPs was found capable of interaction with the delta and kappa opioid receptors, suggesting that they may represent general opioid receptor interacting proteins (ORIPS). Expression of several MORIPs was altered in specific mouse brain regions after chronic treatment with morphine, suggesting that these proteins may play a role in response to opioid agonist drugs. Based on the known function of these newly identified MORIPs, the interactions forming the MOR signalplex are hypothesized to be important for MOR signaling and intracellular trafficking. Understanding the molecular complexity of MOR/MORIP interactions provides a conceptual framework for defining the cellular mechanisms of MOR signaling in brain and may be critical for determining the physiological basis of opioid tolerance and addiction.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067608</identifier><identifier>PMID: 23840749</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Addictions ; Analgesics ; Analgesics, Opioid - metabolism ; Analgesics, Opioid - pharmacology ; Animals ; Biochemistry ; Biology ; Brain ; Brain - drug effects ; Brain - metabolism ; Cell Line ; Deoxyribonucleic acid ; DNA ; Drug abuse ; Drug tolerance ; Drugs ; Female ; Fentanyl ; G protein-coupled receptors ; Health education ; HEK293 Cells ; Heroin ; Humans ; Identification methods ; Immunoprecipitation ; Immunoprecipitation - methods ; Internal medicine ; Intracellular signalling ; Kinases ; Localization ; Medicine ; Mice ; Mice, Inbred C57BL ; Morphine ; Morphine - pharmacology ; Narcotics ; Nuclear Proteins - metabolism ; Opioid receptors (type delta) ; Opioid receptors (type kappa) ; Opioid receptors (type mu) ; Pain ; Pharmacology ; Physics ; Proteins ; Receptors ; Receptors, Opioid, delta - metabolism ; Receptors, Opioid, kappa - metabolism ; Receptors, Opioid, mu - metabolism ; Signal Transduction - drug effects ; Transcription factors ; Two-Hybrid System Techniques ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination - drug effects ; Yeast ; Yeasts - metabolism</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e67608</ispartof><rights>2013 Petko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Petko et al 2013 Petko et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-cd4aeb8066ce64bbb25a829b99dcf48be8201f6c04dd8fb6a3f09c32dbcd8a903</citedby><cites>FETCH-LOGICAL-c526t-cd4aeb8066ce64bbb25a829b99dcf48be8201f6c04dd8fb6a3f09c32dbcd8a903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695902/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695902/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23840749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Harvey, Brandon K.</contributor><creatorcontrib>Petko, Jessica</creatorcontrib><creatorcontrib>Justice-Bitner, Stephanie</creatorcontrib><creatorcontrib>Jin, Jay</creatorcontrib><creatorcontrib>Wong, Victoria</creatorcontrib><creatorcontrib>Kittanakom, Saranya</creatorcontrib><creatorcontrib>Ferraro, Thomas N</creatorcontrib><creatorcontrib>Stagljar, Igor</creatorcontrib><creatorcontrib>Levenson, Robert</creatorcontrib><title>MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening methods to identify a cohort of novel MOR interacting proteins (MORIPs). The interaction between the MOR and a subset of MORIPs was validated in pulldown, co-immunoprecipitation, and co-localization studies using HEK293 cells stably expressing the MOR as well as rodent brain. Additionally, a subset of MORIPs was found capable of interaction with the delta and kappa opioid receptors, suggesting that they may represent general opioid receptor interacting proteins (ORIPS). Expression of several MORIPs was altered in specific mouse brain regions after chronic treatment with morphine, suggesting that these proteins may play a role in response to opioid agonist drugs. Based on the known function of these newly identified MORIPs, the interactions forming the MOR signalplex are hypothesized to be important for MOR signaling and intracellular trafficking. Understanding the molecular complexity of MOR/MORIP interactions provides a conceptual framework for defining the cellular mechanisms of MOR signaling in brain and may be critical for determining the physiological basis of opioid tolerance and addiction.</description><subject>Addictions</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - metabolism</subject><subject>Analgesics, Opioid - pharmacology</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cell Line</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug abuse</subject><subject>Drug tolerance</subject><subject>Drugs</subject><subject>Female</subject><subject>Fentanyl</subject><subject>G protein-coupled receptors</subject><subject>Health education</subject><subject>HEK293 Cells</subject><subject>Heroin</subject><subject>Humans</subject><subject>Identification methods</subject><subject>Immunoprecipitation</subject><subject>Immunoprecipitation - methods</subject><subject>Internal medicine</subject><subject>Intracellular signalling</subject><subject>Kinases</subject><subject>Localization</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Narcotics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Opioid receptors (type delta)</subject><subject>Opioid receptors (type kappa)</subject><subject>Opioid receptors (type mu)</subject><subject>Pain</subject><subject>Pharmacology</subject><subject>Physics</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Opioid, delta - metabolism</subject><subject>Receptors, Opioid, kappa - metabolism</subject><subject>Receptors, Opioid, mu - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Transcription factors</subject><subject>Two-Hybrid System Techniques</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination - drug effects</subject><subject>Yeast</subject><subject>Yeasts - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1kttuEzEQhlcIREvhDRBY4nqDDxuvzQVSVVGoVFQJwbXlw2ziaGMvtrcoz8EL1yFp1V5w5fHMP9-Mfk3TvCV4QVhPPm7inIIeF1MMsMCY9xyLZ80pkYy2nGL2_FF80rzKeYPxkgnOXzYnlIkO9508bf5-v_mBfEYhFgQhzqv1J-QdhOIHb3XxMaA41OotjGg7t3Hy0TuUwMJUYkI-FEjaFh9WaEqxgA8ZzXn_LUk7vwfoEeng0Da6yoQawNYkHQDtQOeCyp_YrncmVWy2CSDk182LQY8Z3hzfs-bX5ZefF9_a65uvVxfn161dUl5a6zoNRmDOLfDOGEOXWlBppHR26IQBQTEZuMWdc2IwXLMBS8uoM9YJLTE7a94fuNMYszr6mVV1l7JltYdVxdVB4aLeqCn5rU47FbVX_xIxrZROxdsR1NCBJIJQoR2tw6WhPSauZwxrQg3TlfX5OG02W3C2epz0-AT6tBL8Wq3irWJcLiWmFfDhCEjx9wy5_Gfl7qCyKeacYHiYQPBeR-671P5w1PFwatu7x9s9NN1fCrsDFVrGVA</recordid><startdate>20130628</startdate><enddate>20130628</enddate><creator>Petko, Jessica</creator><creator>Justice-Bitner, Stephanie</creator><creator>Jin, Jay</creator><creator>Wong, Victoria</creator><creator>Kittanakom, Saranya</creator><creator>Ferraro, Thomas N</creator><creator>Stagljar, Igor</creator><creator>Levenson, Robert</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130628</creationdate><title>MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens</title><author>Petko, Jessica ; Justice-Bitner, Stephanie ; Jin, Jay ; Wong, Victoria ; Kittanakom, Saranya ; Ferraro, Thomas N ; Stagljar, Igor ; Levenson, Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-cd4aeb8066ce64bbb25a829b99dcf48be8201f6c04dd8fb6a3f09c32dbcd8a903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Addictions</topic><topic>Analgesics</topic><topic>Analgesics, Opioid - metabolism</topic><topic>Analgesics, Opioid - pharmacology</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Brain</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cell Line</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Drug abuse</topic><topic>Drug tolerance</topic><topic>Drugs</topic><topic>Female</topic><topic>Fentanyl</topic><topic>G protein-coupled receptors</topic><topic>Health education</topic><topic>HEK293 Cells</topic><topic>Heroin</topic><topic>Humans</topic><topic>Identification methods</topic><topic>Immunoprecipitation</topic><topic>Immunoprecipitation - methods</topic><topic>Internal medicine</topic><topic>Intracellular signalling</topic><topic>Kinases</topic><topic>Localization</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Narcotics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Opioid receptors (type delta)</topic><topic>Opioid receptors (type kappa)</topic><topic>Opioid receptors (type mu)</topic><topic>Pain</topic><topic>Pharmacology</topic><topic>Physics</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Receptors, Opioid, delta - metabolism</topic><topic>Receptors, Opioid, kappa - metabolism</topic><topic>Receptors, Opioid, mu - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Transcription factors</topic><topic>Two-Hybrid System Techniques</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitination - drug effects</topic><topic>Yeast</topic><topic>Yeasts - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petko, Jessica</creatorcontrib><creatorcontrib>Justice-Bitner, Stephanie</creatorcontrib><creatorcontrib>Jin, Jay</creatorcontrib><creatorcontrib>Wong, Victoria</creatorcontrib><creatorcontrib>Kittanakom, Saranya</creatorcontrib><creatorcontrib>Ferraro, Thomas N</creatorcontrib><creatorcontrib>Stagljar, Igor</creatorcontrib><creatorcontrib>Levenson, Robert</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petko, Jessica</au><au>Justice-Bitner, Stephanie</au><au>Jin, Jay</au><au>Wong, Victoria</au><au>Kittanakom, Saranya</au><au>Ferraro, Thomas N</au><au>Stagljar, Igor</au><au>Levenson, Robert</au><au>Harvey, Brandon K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-28</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e67608</spage><pages>e67608-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening methods to identify a cohort of novel MOR interacting proteins (MORIPs). The interaction between the MOR and a subset of MORIPs was validated in pulldown, co-immunoprecipitation, and co-localization studies using HEK293 cells stably expressing the MOR as well as rodent brain. Additionally, a subset of MORIPs was found capable of interaction with the delta and kappa opioid receptors, suggesting that they may represent general opioid receptor interacting proteins (ORIPS). Expression of several MORIPs was altered in specific mouse brain regions after chronic treatment with morphine, suggesting that these proteins may play a role in response to opioid agonist drugs. Based on the known function of these newly identified MORIPs, the interactions forming the MOR signalplex are hypothesized to be important for MOR signaling and intracellular trafficking. Understanding the molecular complexity of MOR/MORIP interactions provides a conceptual framework for defining the cellular mechanisms of MOR signaling in brain and may be critical for determining the physiological basis of opioid tolerance and addiction.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23840749</pmid><doi>10.1371/journal.pone.0067608</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-06, Vol.8 (6), p.e67608 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1372350743 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Addictions Analgesics Analgesics, Opioid - metabolism Analgesics, Opioid - pharmacology Animals Biochemistry Biology Brain Brain - drug effects Brain - metabolism Cell Line Deoxyribonucleic acid DNA Drug abuse Drug tolerance Drugs Female Fentanyl G protein-coupled receptors Health education HEK293 Cells Heroin Humans Identification methods Immunoprecipitation Immunoprecipitation - methods Internal medicine Intracellular signalling Kinases Localization Medicine Mice Mice, Inbred C57BL Morphine Morphine - pharmacology Narcotics Nuclear Proteins - metabolism Opioid receptors (type delta) Opioid receptors (type kappa) Opioid receptors (type mu) Pain Pharmacology Physics Proteins Receptors Receptors, Opioid, delta - metabolism Receptors, Opioid, kappa - metabolism Receptors, Opioid, mu - metabolism Signal Transduction - drug effects Transcription factors Two-Hybrid System Techniques Ubiquitin-Protein Ligases - metabolism Ubiquitination - drug effects Yeast Yeasts - metabolism |
| title | MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T04%3A43%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MOR%20is%20not%20enough:%20identification%20of%20novel%20mu-opioid%20receptor%20interacting%20proteins%20using%20traditional%20and%20modified%20membrane%20yeast%20two-hybrid%20screens&rft.jtitle=PloS%20one&rft.au=Petko,%20Jessica&rft.date=2013-06-28&rft.volume=8&rft.issue=6&rft.spage=e67608&rft.pages=e67608-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0067608&rft_dat=%3Cproquest_plos_%3E3007994371%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1372350743&rft_id=info:pmid/23840749&rft_doaj_id=oai_doaj_org_article_f4e918128ad248b9b2701d7330a12b3a&rfr_iscdi=true |