Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development
We provide evidence that the sphingolipid ceramide, in addition to its pro-apoptotic function, regulates neural progenitor (NP) motility in vitro and brain development in vivo. Ceramide (N-palmitoyl d-erythro sphingosine and N-oleoyl d-erythro sphingosine) and the ceramide analog N-oleoyl serinol (S...
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| Veröffentlicht in: | Journal of neurochemistry 2008-07, Vol.106 (2), p.718-733 |
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| creator | Wang, Guanghu Krishnamurthy, Kannan Chiang, Ying-Wei Dasgupta, Somsankar Bieberich, Erhard |
| description | We provide evidence that the sphingolipid ceramide, in addition to its pro-apoptotic function, regulates neural progenitor (NP) motility in vitro and brain development in vivo. Ceramide (N-palmitoyl d-erythro sphingosine and N-oleoyl d-erythro sphingosine) and the ceramide analog N-oleoyl serinol (S18) stimulate migration of NPs in scratch (wounding) migration assays. Sphingolipid depletion by inhibition of de novo ceramide biosynthesis, or ceramide inactivation using an anti-ceramide antibody, obliterates NP motility, which is restored by ceramide or S18. These results suggest that ceramide is crucial for NP motility. Wounding of the NP monolayer activates neutral sphingomyelinase indicating that ceramide is generated from sphingomyelin. In membrane processes, ceramide is co-distributed with its binding partner atypical protein kinase C ζ/λ (aPKC), and Cdc42, α/β-tubulin, and β-catenin, three proteins involved in aPKC-dependent regulation of cell polarity and motility. Sphingolipid depletion by myriocin prevents membrane translocation of aPKC and Cdc42, which is restored by ceramide or S18. These results suggest that ceramide-mediated membrane association of aPKC/Cdc42 is important for NP motility. In vivo, sphingolipid depletion leads to ectopic localization of mitotic or post-mitotic neural cells in the embryonic brain, while S18 restores the normal brain organization. In summary, our study provides novel evidence that ceramide is critical for NP motility and polarity in vitro and in vivo. |
| doi_str_mv | 10.1111/j.1471-4159.2008.05451.x |
| format | Article |
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Ceramide (N-palmitoyl d-erythro sphingosine and N-oleoyl d-erythro sphingosine) and the ceramide analog N-oleoyl serinol (S18) stimulate migration of NPs in scratch (wounding) migration assays. Sphingolipid depletion by inhibition of de novo ceramide biosynthesis, or ceramide inactivation using an anti-ceramide antibody, obliterates NP motility, which is restored by ceramide or S18. These results suggest that ceramide is crucial for NP motility. Wounding of the NP monolayer activates neutral sphingomyelinase indicating that ceramide is generated from sphingomyelin. In membrane processes, ceramide is co-distributed with its binding partner atypical protein kinase C ζ/λ (aPKC), and Cdc42, α/β-tubulin, and β-catenin, three proteins involved in aPKC-dependent regulation of cell polarity and motility. Sphingolipid depletion by myriocin prevents membrane translocation of aPKC and Cdc42, which is restored by ceramide or S18. These results suggest that ceramide-mediated membrane association of aPKC/Cdc42 is important for NP motility. In vivo, sphingolipid depletion leads to ectopic localization of mitotic or post-mitotic neural cells in the embryonic brain, while S18 restores the normal brain organization. In summary, our study provides novel evidence that ceramide is critical for NP motility and polarity in vitro and in vivo.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.2008.05451.x</identifier><identifier>PMID: 18466329</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Oxford, UK : Blackwell Publishing Ltd</publisher><subject>Actins - metabolism ; Animals ; Antibodies - pharmacology ; beta Catenin - metabolism ; Biochemistry ; Biochemistry and metabolism ; Biological and medical sciences ; Brain ; brain morphogenesis ; cdc42 GTP-Binding Protein - metabolism ; Cell Differentiation - drug effects ; Cell Movement - drug effects ; Cell Polarity - drug effects ; Cells, Cultured ; Cellular biology ; Central nervous system ; ceramide ; Ceramides - immunology ; Ceramides - pharmacology ; Development. Senescence. Regeneration. Transplantation ; Embryo, Mammalian ; Fatty Acids, Monounsaturated - pharmacology ; Fundamental and applied biological sciences. Psychology ; Immunosuppressive Agents - pharmacology ; Mice ; motility ; Neurology ; Neurons - physiology ; Oleic Acids - pharmacology ; polarity ; Propylene Glycols - pharmacology ; Protein Binding - drug effects ; Protein Binding - physiology ; Protein Kinase C - metabolism ; Protein Transport - drug effects ; Rodents ; sphingolipids ; Stem Cells - drug effects ; Tubulin - metabolism ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of neurochemistry, 2008-07, Vol.106 (2), p.718-733</ispartof><rights>2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry</rights><rights>2008 INIST-CNRS</rights><rights>Journal compilation © 2008 International Society for Neurochemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c7051-aea078614b289c10c490a17f430f4148852cf5646554b36c6a6b1a4459f09b663</citedby><cites>FETCH-LOGICAL-c7051-aea078614b289c10c490a17f430f4148852cf5646554b36c6a6b1a4459f09b663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.2008.05451.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.2008.05451.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,782,786,887,1419,1435,27931,27932,45581,45582,46416,46840</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20498689$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18466329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Guanghu</creatorcontrib><creatorcontrib>Krishnamurthy, Kannan</creatorcontrib><creatorcontrib>Chiang, Ying-Wei</creatorcontrib><creatorcontrib>Dasgupta, Somsankar</creatorcontrib><creatorcontrib>Bieberich, Erhard</creatorcontrib><title>Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>We provide evidence that the sphingolipid ceramide, in addition to its pro-apoptotic function, regulates neural progenitor (NP) motility in vitro and brain development in vivo. Ceramide (N-palmitoyl d-erythro sphingosine and N-oleoyl d-erythro sphingosine) and the ceramide analog N-oleoyl serinol (S18) stimulate migration of NPs in scratch (wounding) migration assays. Sphingolipid depletion by inhibition of de novo ceramide biosynthesis, or ceramide inactivation using an anti-ceramide antibody, obliterates NP motility, which is restored by ceramide or S18. These results suggest that ceramide is crucial for NP motility. Wounding of the NP monolayer activates neutral sphingomyelinase indicating that ceramide is generated from sphingomyelin. In membrane processes, ceramide is co-distributed with its binding partner atypical protein kinase C ζ/λ (aPKC), and Cdc42, α/β-tubulin, and β-catenin, three proteins involved in aPKC-dependent regulation of cell polarity and motility. Sphingolipid depletion by myriocin prevents membrane translocation of aPKC and Cdc42, which is restored by ceramide or S18. These results suggest that ceramide-mediated membrane association of aPKC/Cdc42 is important for NP motility. In vivo, sphingolipid depletion leads to ectopic localization of mitotic or post-mitotic neural cells in the embryonic brain, while S18 restores the normal brain organization. In summary, our study provides novel evidence that ceramide is critical for NP motility and polarity in vitro and in vivo.</description><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Antibodies - pharmacology</subject><subject>beta Catenin - metabolism</subject><subject>Biochemistry</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>brain morphogenesis</subject><subject>cdc42 GTP-Binding Protein - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Movement - drug effects</subject><subject>Cell Polarity - drug effects</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Central nervous system</subject><subject>ceramide</subject><subject>Ceramides - immunology</subject><subject>Ceramides - pharmacology</subject><subject>Development. Senescence. Regeneration. Transplantation</subject><subject>Embryo, Mammalian</subject><subject>Fatty Acids, Monounsaturated - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Mice</subject><subject>motility</subject><subject>Neurology</subject><subject>Neurons - physiology</subject><subject>Oleic Acids - pharmacology</subject><subject>polarity</subject><subject>Propylene Glycols - pharmacology</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - physiology</subject><subject>Protein Kinase C - metabolism</subject><subject>Protein Transport - drug effects</subject><subject>Rodents</subject><subject>sphingolipids</subject><subject>Stem Cells - drug effects</subject><subject>Tubulin - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV2P1CAUhhujccfVv6DERO9az6FA6YUmZuJnNpqoe00oQ0cmbelCu-78e-nOZPy4UW4gnOc98J43ywhCgWm92BXIKswZ8rqgALIAzjgWN3ey1alwN1sBUJqXwOhZ9iDGHQAKJvB-doaSCVHSepWNX-x27vTk_EB8SwY7B92RMfitHdzkAzG260jvJ9e5aU-afboIuncbS_SwIaOf7DC5JHH92Dlz2yiSNgl7P0dLmqDdQDb22nZ-7BP7MLvX6i7aR8f9PLt8--bb-n1-8fndh_Xri9xUwDHXVkMlBbKGytogGFaDxqplJbQMmZScmpYnO5yzphRGaNGgZozXLdRNMneevTr0HeemtxuTnk7O1Bhcr8Neee3Un5XBfVdbf61KiVRULDV4fmwQ_NVs46R6F5dp6MEma0rUDBgi_ydIQVYCZZXAp3-BOz-HIU0hMckI0HqB5AEywccYbHv6MoJawlc7tWSslozVEr66DV_dJOnj3y3_Eh7TTsCzI6Cj0V0b9GBcPHEUWC2FXLiXB-6H6-z-vz-gPn5aL6ekf3LQt9orvQ3pjcuvFLAEqJFzQcufiMDU8Q</recordid><startdate>200807</startdate><enddate>200807</enddate><creator>Wang, Guanghu</creator><creator>Krishnamurthy, Kannan</creator><creator>Chiang, Ying-Wei</creator><creator>Dasgupta, Somsankar</creator><creator>Bieberich, Erhard</creator><general>Oxford, UK : Blackwell Publishing Ltd</general><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>FBQ</scope><scope>IQODW</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>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><scope>5PM</scope></search><sort><creationdate>200807</creationdate><title>Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development</title><author>Wang, Guanghu ; Krishnamurthy, Kannan ; Chiang, Ying-Wei ; Dasgupta, Somsankar ; Bieberich, Erhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c7051-aea078614b289c10c490a17f430f4148852cf5646554b36c6a6b1a4459f09b663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Antibodies - pharmacology</topic><topic>beta Catenin - metabolism</topic><topic>Biochemistry</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>brain morphogenesis</topic><topic>cdc42 GTP-Binding Protein - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Movement - drug effects</topic><topic>Cell Polarity - drug effects</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Central nervous system</topic><topic>ceramide</topic><topic>Ceramides - immunology</topic><topic>Ceramides - pharmacology</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>Embryo, Mammalian</topic><topic>Fatty Acids, Monounsaturated - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Mice</topic><topic>motility</topic><topic>Neurology</topic><topic>Neurons - physiology</topic><topic>Oleic Acids - pharmacology</topic><topic>polarity</topic><topic>Propylene Glycols - pharmacology</topic><topic>Protein Binding - drug effects</topic><topic>Protein Binding - physiology</topic><topic>Protein Kinase C - metabolism</topic><topic>Protein Transport - drug effects</topic><topic>Rodents</topic><topic>sphingolipids</topic><topic>Stem Cells - drug effects</topic><topic>Tubulin - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Guanghu</creatorcontrib><creatorcontrib>Krishnamurthy, Kannan</creatorcontrib><creatorcontrib>Chiang, Ying-Wei</creatorcontrib><creatorcontrib>Dasgupta, Somsankar</creatorcontrib><creatorcontrib>Bieberich, Erhard</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Guanghu</au><au>Krishnamurthy, Kannan</au><au>Chiang, Ying-Wei</au><au>Dasgupta, Somsankar</au><au>Bieberich, Erhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2008-07</date><risdate>2008</risdate><volume>106</volume><issue>2</issue><spage>718</spage><epage>733</epage><pages>718-733</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>We provide evidence that the sphingolipid ceramide, in addition to its pro-apoptotic function, regulates neural progenitor (NP) motility in vitro and brain development in vivo. Ceramide (N-palmitoyl d-erythro sphingosine and N-oleoyl d-erythro sphingosine) and the ceramide analog N-oleoyl serinol (S18) stimulate migration of NPs in scratch (wounding) migration assays. Sphingolipid depletion by inhibition of de novo ceramide biosynthesis, or ceramide inactivation using an anti-ceramide antibody, obliterates NP motility, which is restored by ceramide or S18. These results suggest that ceramide is crucial for NP motility. Wounding of the NP monolayer activates neutral sphingomyelinase indicating that ceramide is generated from sphingomyelin. In membrane processes, ceramide is co-distributed with its binding partner atypical protein kinase C ζ/λ (aPKC), and Cdc42, α/β-tubulin, and β-catenin, three proteins involved in aPKC-dependent regulation of cell polarity and motility. Sphingolipid depletion by myriocin prevents membrane translocation of aPKC and Cdc42, which is restored by ceramide or S18. These results suggest that ceramide-mediated membrane association of aPKC/Cdc42 is important for NP motility. In vivo, sphingolipid depletion leads to ectopic localization of mitotic or post-mitotic neural cells in the embryonic brain, while S18 restores the normal brain organization. In summary, our study provides novel evidence that ceramide is critical for NP motility and polarity in vitro and in vivo.</abstract><cop>Oxford, UK</cop><pub>Oxford, UK : Blackwell Publishing Ltd</pub><pmid>18466329</pmid><doi>10.1111/j.1471-4159.2008.05451.x</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - metabolism Animals Antibodies - pharmacology beta Catenin - metabolism Biochemistry Biochemistry and metabolism Biological and medical sciences Brain brain morphogenesis cdc42 GTP-Binding Protein - metabolism Cell Differentiation - drug effects Cell Movement - drug effects Cell Polarity - drug effects Cells, Cultured Cellular biology Central nervous system ceramide Ceramides - immunology Ceramides - pharmacology Development. Senescence. Regeneration. Transplantation Embryo, Mammalian Fatty Acids, Monounsaturated - pharmacology Fundamental and applied biological sciences. Psychology Immunosuppressive Agents - pharmacology Mice motility Neurology Neurons - physiology Oleic Acids - pharmacology polarity Propylene Glycols - pharmacology Protein Binding - drug effects Protein Binding - physiology Protein Kinase C - metabolism Protein Transport - drug effects Rodents sphingolipids Stem Cells - drug effects Tubulin - metabolism Vertebrates: nervous system and sense organs |
| title | Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development |
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