Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons
We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of th...
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| Veröffentlicht in: | Journal of neurochemistry 2013-02, Vol.124 (4), p.502-513 |
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| creator | Kim, Han‐Gyu Lee, Choong‐Ku Cho, Sung‐Min Whang, Kum Cha, Byong‐Ho Shin, Ju‐Hyun Song, Ki‐Hak Jeong, Seong‐Woo |
| description | We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1β significantly increased the transcript and protein level of the nAChR α3 and β4 subunits. Consistent with these molecular data, nicotinic currents (IACh) were significantly up‐regulated in NRG1β‐treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the IACh. Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1β on the IACh. Stimulation of the ErbB receptors by NRG1β activated the phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K‐mediated activation of Akt preceded Erk1/2 activation in NRG1β‐treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up‐regulates nAChR expression via the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade and may be involved in maintaining the ACh‐mediated synaptic transmission in adult autonomic ganglia.
Neuregulin 1 (NRG1) is critical for formation of the autonomic nicotinic synapseduring development. However, the functional role of NRG1 in adult autonomic neurons remains unknown. We found NRG1‐mediated up‐regulation of the nicotinic acetylcholine receptor via the ErbB2/ErbB3‐PI3K‐MAPK signaling in MPG neurons of adult rat. This finding suggests that NRG1 is also required for maintenance of adult autonomic nicotinic synapse. |
| doi_str_mv | 10.1111/jnc.12109 |
| format | Article |
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Neuregulin 1 (NRG1) is critical for formation of the autonomic nicotinic synapseduring development. However, the functional role of NRG1 in adult autonomic neurons remains unknown. We found NRG1‐mediated up‐regulation of the nicotinic acetylcholine receptor via the ErbB2/ErbB3‐PI3K‐MAPK signaling in MPG neurons of adult rat. This finding suggests that NRG1 is also required for maintenance of adult autonomic nicotinic synapse.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/jnc.12109</identifier><identifier>PMID: 23199222</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acetylcholine - pharmacology ; Animals ; autonomic ganglion ; Cycloheximide - pharmacology ; Enzyme Inhibitors - pharmacology ; Epidermal growth factor ; ErbB ; Ganglia, Autonomic - cytology ; Male ; MAP Kinase Signaling System - drug effects ; MAPK ; Membrane Potentials - drug effects ; Membrane Potentials - genetics ; Mitogen-Activated Protein Kinase 3 - genetics ; Mitogen-Activated Protein Kinase 3 - metabolism ; neuregulin ; Neuregulin-1 - pharmacology ; Neurochemistry ; Neurons ; Neurons - drug effects ; nicotinic acetylcholine receptor ; Patch-Clamp Techniques ; Phosphorylation ; PI3K ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Synthesis Inhibitors - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; Receptor, ErbB-3 - genetics ; Receptor, ErbB-3 - metabolism ; Receptors, Nicotinic - metabolism ; Signal transduction ; Time Factors ; Up-Regulation - drug effects</subject><ispartof>Journal of neurochemistry, 2013-02, Vol.124 (4), p.502-513</ispartof><rights>2012 International Society for Neurochemistry</rights><rights>2012 International Society for Neurochemistry.</rights><rights>Copyright © 2013 International Society for Neurochemistry</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjnc.12109$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjnc.12109$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,1434,27926,27927,45576,45577,46411,46835</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23199222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Han‐Gyu</creatorcontrib><creatorcontrib>Lee, Choong‐Ku</creatorcontrib><creatorcontrib>Cho, Sung‐Min</creatorcontrib><creatorcontrib>Whang, Kum</creatorcontrib><creatorcontrib>Cha, Byong‐Ho</creatorcontrib><creatorcontrib>Shin, Ju‐Hyun</creatorcontrib><creatorcontrib>Song, Ki‐Hak</creatorcontrib><creatorcontrib>Jeong, Seong‐Woo</creatorcontrib><title>Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1β significantly increased the transcript and protein level of the nAChR α3 and β4 subunits. Consistent with these molecular data, nicotinic currents (IACh) were significantly up‐regulated in NRG1β‐treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the IACh. Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1β on the IACh. Stimulation of the ErbB receptors by NRG1β activated the phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K‐mediated activation of Akt preceded Erk1/2 activation in NRG1β‐treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up‐regulates nAChR expression via the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade and may be involved in maintaining the ACh‐mediated synaptic transmission in adult autonomic ganglia.
Neuregulin 1 (NRG1) is critical for formation of the autonomic nicotinic synapseduring development. However, the functional role of NRG1 in adult autonomic neurons remains unknown. We found NRG1‐mediated up‐regulation of the nicotinic acetylcholine receptor via the ErbB2/ErbB3‐PI3K‐MAPK signaling in MPG neurons of adult rat. This finding suggests that NRG1 is also required for maintenance of adult autonomic nicotinic synapse.</description><subject>Acetylcholine - pharmacology</subject><subject>Animals</subject><subject>autonomic ganglion</subject><subject>Cycloheximide - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Epidermal growth factor</subject><subject>ErbB</subject><subject>Ganglia, Autonomic - cytology</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAPK</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - genetics</subject><subject>Mitogen-Activated Protein Kinase 3 - genetics</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>neuregulin</subject><subject>Neuregulin-1 - pharmacology</subject><subject>Neurochemistry</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>nicotinic acetylcholine receptor</subject><subject>Patch-Clamp Techniques</subject><subject>Phosphorylation</subject><subject>PI3K</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Receptor, ErbB-3 - genetics</subject><subject>Receptor, ErbB-3 - metabolism</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Signal transduction</subject><subject>Time Factors</subject><subject>Up-Regulation - drug effects</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUs1u1DAQthCILoUDL4AsceGSrj2OnfhYVgVKS-kBzpHXmc1mlbWDHQv2xiPwHrwVT4I3LRw44cPMWP5-rJkh5DlnZzyf5c7ZMw6c6QdkwcuKFyWX-iFZMAZQCFbCCXkS444xrkrFH5MTEFxrAFiQnzeYAnZp6B3lNI2_vv-Yr2bCSKctUvw2Boyx9476DXW99VOfIzUWp8Ngtz4zkQa0OE4-HDnBp247cy_C-jUsj1Fk3dtLcZXTh_PbKxr7zpnM7Kg10ZoWafY3bRomatLknd9ni864bjgau_xH7-JT8mhjhojP7vMp-fzm4tPqXXH98e3l6vy6GAUHXSitdFvBBjctl22laiNzwayq6spYltskZKsBW7FmYEGYtcBSSSYFaOCqEqfk1Z3uGPyXhHFq9n20OAzGoU-x4YJLBdnqP6BQg-SymlVf_gPd-RRyF2ZUnoeo6jqjXtyj0nqPbTOGfm_CofkzsQxY3gG-9gMe_r5z1hxXocmr0Myr0Ly_Wc2F-A1-8qjO</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Kim, Han‐Gyu</creator><creator>Lee, Choong‐Ku</creator><creator>Cho, Sung‐Min</creator><creator>Whang, Kum</creator><creator>Cha, Byong‐Ho</creator><creator>Shin, Ju‐Hyun</creator><creator>Song, Ki‐Hak</creator><creator>Jeong, Seong‐Woo</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201302</creationdate><title>Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons</title><author>Kim, Han‐Gyu ; Lee, Choong‐Ku ; Cho, Sung‐Min ; Whang, Kum ; Cha, Byong‐Ho ; Shin, Ju‐Hyun ; Song, Ki‐Hak ; Jeong, Seong‐Woo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3129-6969d72fefd15d768a5d150c6787ac010935d92ed3b02c23ab3e4650532921673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetylcholine - pharmacology</topic><topic>Animals</topic><topic>autonomic ganglion</topic><topic>Cycloheximide - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Epidermal growth factor</topic><topic>ErbB</topic><topic>Ganglia, Autonomic - cytology</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAPK</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - genetics</topic><topic>Mitogen-Activated Protein Kinase 3 - genetics</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>neuregulin</topic><topic>Neuregulin-1 - pharmacology</topic><topic>Neurochemistry</topic><topic>Neurons</topic><topic>Neurons - drug effects</topic><topic>nicotinic acetylcholine receptor</topic><topic>Patch-Clamp Techniques</topic><topic>Phosphorylation</topic><topic>PI3K</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Synthesis Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Receptor, ErbB-3 - genetics</topic><topic>Receptor, ErbB-3 - metabolism</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Signal transduction</topic><topic>Time Factors</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Han‐Gyu</creatorcontrib><creatorcontrib>Lee, Choong‐Ku</creatorcontrib><creatorcontrib>Cho, Sung‐Min</creatorcontrib><creatorcontrib>Whang, Kum</creatorcontrib><creatorcontrib>Cha, Byong‐Ho</creatorcontrib><creatorcontrib>Shin, Ju‐Hyun</creatorcontrib><creatorcontrib>Song, Ki‐Hak</creatorcontrib><creatorcontrib>Jeong, Seong‐Woo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Han‐Gyu</au><au>Lee, Choong‐Ku</au><au>Cho, Sung‐Min</au><au>Whang, Kum</au><au>Cha, Byong‐Ho</au><au>Shin, Ju‐Hyun</au><au>Song, Ki‐Hak</au><au>Jeong, Seong‐Woo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2013-02</date><risdate>2013</risdate><volume>124</volume><issue>4</issue><spage>502</spage><epage>513</epage><pages>502-513</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1β significantly increased the transcript and protein level of the nAChR α3 and β4 subunits. Consistent with these molecular data, nicotinic currents (IACh) were significantly up‐regulated in NRG1β‐treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the IACh. Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1β on the IACh. Stimulation of the ErbB receptors by NRG1β activated the phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K‐mediated activation of Akt preceded Erk1/2 activation in NRG1β‐treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up‐regulates nAChR expression via the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade and may be involved in maintaining the ACh‐mediated synaptic transmission in adult autonomic ganglia.
Neuregulin 1 (NRG1) is critical for formation of the autonomic nicotinic synapseduring development. However, the functional role of NRG1 in adult autonomic neurons remains unknown. We found NRG1‐mediated up‐regulation of the nicotinic acetylcholine receptor via the ErbB2/ErbB3‐PI3K‐MAPK signaling in MPG neurons of adult rat. This finding suggests that NRG1 is also required for maintenance of adult autonomic nicotinic synapse.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23199222</pmid><doi>10.1111/jnc.12109</doi><tpages>12</tpages></addata></record> |
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| subjects | Acetylcholine - pharmacology Animals autonomic ganglion Cycloheximide - pharmacology Enzyme Inhibitors - pharmacology Epidermal growth factor ErbB Ganglia, Autonomic - cytology Male MAP Kinase Signaling System - drug effects MAPK Membrane Potentials - drug effects Membrane Potentials - genetics Mitogen-Activated Protein Kinase 3 - genetics Mitogen-Activated Protein Kinase 3 - metabolism neuregulin Neuregulin-1 - pharmacology Neurochemistry Neurons Neurons - drug effects nicotinic acetylcholine receptor Patch-Clamp Techniques Phosphorylation PI3K Protein Isoforms - genetics Protein Isoforms - metabolism Protein Synthesis Inhibitors - pharmacology Rats Rats, Sprague-Dawley Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Receptor, ErbB-3 - genetics Receptor, ErbB-3 - metabolism Receptors, Nicotinic - metabolism Signal transduction Time Factors Up-Regulation - drug effects |
| title | Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons |
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