NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling
Although glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is essential for enteric nervous system (ENS) development, the positive regulators regulating GDNF/Ret signaling and controlling ENS development are poorly understood. Here, we show that Nedd4-related E3 ubiquitin ligase-2 (NE...
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| Veröffentlicht in: | Cellular signalling 2015-03, Vol.27 (3), p.578-586 |
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| container_title | Cellular signalling |
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| creator | Wei, Rongfei Qiu, Xiao Wang, Shaoxia Li, Yang Wang, Yiwu Lu, Kefeng Fu, Yesheng Xing, Guichun He, Fuchu Zhang, Lingqiang |
| description | Although glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is essential for enteric nervous system (ENS) development, the positive regulators regulating GDNF/Ret signaling and controlling ENS development are poorly understood. Here, we show that Nedd4-related E3 ubiquitin ligase-2 (NEDL2) plays an essential and positive physiological role in regulating ENS development and GDNF/Ret signaling. All of the NEDL2-deficient mice die within 2weeks after birth, showing low body weight. These mice showed a progressive bowel motility defect resulting from intestinal aganglionosis. We show that NEDL2 positively regulates enteric neural precursor proliferation through the GDNF/Akt signaling pathway. Together, these findings unveil the physiological function of NEDL2 in vivo.
•We firstly generate NEDL2 knockout mice model.•All the NEDL2-deficient mice die within 2weeks after birth with low body weight.•NEDL2-deficient mice showed a progressive bowel motility defect.•The number of enteric neurons was decreased in NEDL2−/− mice.•NEDL2−/− mice exhibited decreased GDNF/Ret signaling activation. |
| doi_str_mv | 10.1016/j.cellsig.2014.12.013 |
| format | Article |
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•We firstly generate NEDL2 knockout mice model.•All the NEDL2-deficient mice die within 2weeks after birth with low body weight.•NEDL2-deficient mice showed a progressive bowel motility defect.•The number of enteric neurons was decreased in NEDL2−/− mice.•NEDL2−/− mice exhibited decreased GDNF/Ret signaling activation.</description><identifier>ISSN: 0898-6568</identifier><identifier>EISSN: 1873-3913</identifier><identifier>DOI: 10.1016/j.cellsig.2014.12.013</identifier><identifier>PMID: 25555806</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Animals ; Enteric nervous system ; GDNF/Ret signaling ; Glial Cell Line-Derived Neurotrophic Factor - genetics ; Glial Cell Line-Derived Neurotrophic Factor - metabolism ; Intestines - pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Mouse ; NEDL2 ; Phosphorylation ; Proto-Oncogene Proteins c-akt - metabolism ; Proto-Oncogene Proteins c-ret - metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases - deficiency ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism</subject><ispartof>Cellular signalling, 2015-03, Vol.27 (3), p.578-586</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-17bc6694d50f0372ace09ce66a1f8f824be090f0760faff1db15dbfd3728bfea3</citedby><cites>FETCH-LOGICAL-c501t-17bc6694d50f0372ace09ce66a1f8f824be090f0760faff1db15dbfd3728bfea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S089865681400415X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25555806$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Rongfei</creatorcontrib><creatorcontrib>Qiu, Xiao</creatorcontrib><creatorcontrib>Wang, Shaoxia</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Wang, Yiwu</creatorcontrib><creatorcontrib>Lu, Kefeng</creatorcontrib><creatorcontrib>Fu, Yesheng</creatorcontrib><creatorcontrib>Xing, Guichun</creatorcontrib><creatorcontrib>He, Fuchu</creatorcontrib><creatorcontrib>Zhang, Lingqiang</creatorcontrib><title>NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling</title><title>Cellular signalling</title><addtitle>Cell Signal</addtitle><description>Although glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is essential for enteric nervous system (ENS) development, the positive regulators regulating GDNF/Ret signaling and controlling ENS development are poorly understood. Here, we show that Nedd4-related E3 ubiquitin ligase-2 (NEDL2) plays an essential and positive physiological role in regulating ENS development and GDNF/Ret signaling. All of the NEDL2-deficient mice die within 2weeks after birth, showing low body weight. These mice showed a progressive bowel motility defect resulting from intestinal aganglionosis. We show that NEDL2 positively regulates enteric neural precursor proliferation through the GDNF/Akt signaling pathway. Together, these findings unveil the physiological function of NEDL2 in vivo.
•We firstly generate NEDL2 knockout mice model.•All the NEDL2-deficient mice die within 2weeks after birth with low body weight.•NEDL2-deficient mice showed a progressive bowel motility defect.•The number of enteric neurons was decreased in NEDL2−/− mice.•NEDL2−/− mice exhibited decreased GDNF/Ret signaling activation.</description><subject>Animals</subject><subject>Enteric nervous system</subject><subject>GDNF/Ret signaling</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - genetics</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - metabolism</subject><subject>Intestines - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Mouse</subject><subject>NEDL2</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Proto-Oncogene Proteins c-ret - metabolism</subject><subject>Signal Transduction</subject><subject>Ubiquitin-Protein Ligases - deficiency</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><issn>0898-6568</issn><issn>1873-3913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PwzAMhiMEYmPwE0A5cmkX9yPtTgixD5CmIaFxjtLEmTJ17UjaSfx7Mm1wxZfI9vva8UPIPbAYGPDxNlZY195u4oRBFkMSM0gvyBDKIo3SCaSXZMjKSRnxnJcDcuP9ljHIGU-uySDJQ5SMD8l6NZsuE2o9lQ1F77HprKypw01fy651tDU01NBZRRvsXehpPGDd7nehHEyaLqar-fgDOxo-08jaNptbcmVk7fHu_I7I53y2fnmNlu-Lt5fnZaRyBl0ERaU4n2Q6Z4alRSIVsolCziWY0pRJVoU8tArOjDQGdAW5rowO0rIyKNMReTzN3bv2q0ffiZ31Ryyywbb3AsLtLOOcF0Gan6TKtd47NGLv7E66bwFMHIGKrTgDFUegAhIRgAbfw3lFX-1Q_7l-CQbB00mA4dCDRSe8stgo1Nah6oRu7T8rfgC4momo</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Wei, Rongfei</creator><creator>Qiu, Xiao</creator><creator>Wang, Shaoxia</creator><creator>Li, Yang</creator><creator>Wang, Yiwu</creator><creator>Lu, Kefeng</creator><creator>Fu, Yesheng</creator><creator>Xing, Guichun</creator><creator>He, Fuchu</creator><creator>Zhang, Lingqiang</creator><general>Elsevier Inc</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></search><sort><creationdate>20150301</creationdate><title>NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling</title><author>Wei, Rongfei ; Qiu, Xiao ; Wang, Shaoxia ; Li, Yang ; Wang, Yiwu ; Lu, Kefeng ; Fu, Yesheng ; Xing, Guichun ; He, Fuchu ; Zhang, Lingqiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-17bc6694d50f0372ace09ce66a1f8f824be090f0760faff1db15dbfd3728bfea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Enteric nervous system</topic><topic>GDNF/Ret signaling</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - genetics</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - metabolism</topic><topic>Intestines - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Mouse</topic><topic>NEDL2</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Proto-Oncogene Proteins c-ret - metabolism</topic><topic>Signal Transduction</topic><topic>Ubiquitin-Protein Ligases - deficiency</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Rongfei</creatorcontrib><creatorcontrib>Qiu, Xiao</creatorcontrib><creatorcontrib>Wang, Shaoxia</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Wang, Yiwu</creatorcontrib><creatorcontrib>Lu, Kefeng</creatorcontrib><creatorcontrib>Fu, Yesheng</creatorcontrib><creatorcontrib>Xing, Guichun</creatorcontrib><creatorcontrib>He, Fuchu</creatorcontrib><creatorcontrib>Zhang, Lingqiang</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><jtitle>Cellular signalling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Rongfei</au><au>Qiu, Xiao</au><au>Wang, Shaoxia</au><au>Li, Yang</au><au>Wang, Yiwu</au><au>Lu, Kefeng</au><au>Fu, Yesheng</au><au>Xing, Guichun</au><au>He, Fuchu</au><au>Zhang, Lingqiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling</atitle><jtitle>Cellular signalling</jtitle><addtitle>Cell Signal</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>27</volume><issue>3</issue><spage>578</spage><epage>586</epage><pages>578-586</pages><issn>0898-6568</issn><eissn>1873-3913</eissn><abstract>Although glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is essential for enteric nervous system (ENS) development, the positive regulators regulating GDNF/Ret signaling and controlling ENS development are poorly understood. Here, we show that Nedd4-related E3 ubiquitin ligase-2 (NEDL2) plays an essential and positive physiological role in regulating ENS development and GDNF/Ret signaling. All of the NEDL2-deficient mice die within 2weeks after birth, showing low body weight. These mice showed a progressive bowel motility defect resulting from intestinal aganglionosis. We show that NEDL2 positively regulates enteric neural precursor proliferation through the GDNF/Akt signaling pathway. Together, these findings unveil the physiological function of NEDL2 in vivo.
•We firstly generate NEDL2 knockout mice model.•All the NEDL2-deficient mice die within 2weeks after birth with low body weight.•NEDL2-deficient mice showed a progressive bowel motility defect.•The number of enteric neurons was decreased in NEDL2−/− mice.•NEDL2−/− mice exhibited decreased GDNF/Ret signaling activation.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>25555806</pmid><doi>10.1016/j.cellsig.2014.12.013</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Enteric nervous system GDNF/Ret signaling Glial Cell Line-Derived Neurotrophic Factor - genetics Glial Cell Line-Derived Neurotrophic Factor - metabolism Intestines - pathology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Mouse NEDL2 Phosphorylation Proto-Oncogene Proteins c-akt - metabolism Proto-Oncogene Proteins c-ret - metabolism Signal Transduction Ubiquitin-Protein Ligases - deficiency Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism |
| title | NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling |
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