Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth
Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in...
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| Veröffentlicht in: | Nature cell biology 2005-11, Vol.7 (11), p.1124-1132 |
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| creator | Xiong, Wen-Cheng Xie, Yi Ding, Yu-Qiang Hong, Yan Feng, Zhu Navarre, Sammy Xi, Cai-Xia Zhu, Xiao-Juan Wang, Chun-Lei Ackerman, S. L Kozlowski, David Mei, Lin |
| description | Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation. |
| doi_str_mv | 10.1038/ncb1321 |
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L ; Kozlowski, David ; Mei, Lin</creator><creatorcontrib>Xiong, Wen-Cheng ; Xie, Yi ; Ding, Yu-Qiang ; Hong, Yan ; Feng, Zhu ; Navarre, Sammy ; Xi, Cai-Xia ; Zhu, Xiao-Juan ; Wang, Chun-Lei ; Ackerman, S. L ; Kozlowski, David ; Mei, Lin</creatorcontrib><description>Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.</description><identifier>ISSN: 1465-7392</identifier><identifier>ISSN: 1476-4679</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1321</identifier><identifier>PMID: 16244667</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cells, Cultured ; Cellular signal transduction ; Chick Embryo - cytology ; Chick Embryo - metabolism ; Danio rerio ; DCC Receptor ; Developmental Biology ; Humans ; letter ; Life Sciences ; Lipid Metabolism - physiology ; Membrane proteins ; Membrane Proteins - metabolism ; Membrane Proteins - physiology ; Nerve Growth Factors - physiology ; Netrin-1 ; Neurites - metabolism ; Neurons - cytology ; Neurons - metabolism ; Phosphatidylinositol ; Phosphatidylinositol 4,5-Diphosphate - metabolism ; Phospholipid Transfer Proteins - metabolism ; Phospholipid Transfer Proteins - physiology ; Physiological aspects ; Receptors, Cell Surface - metabolism ; Signal Transduction - drug effects ; Stem Cells ; Transfection ; Tumor Suppressor Proteins - metabolism ; Tumor Suppressor Proteins - physiology ; Zebrafish - embryology ; Zebrafish - physiology ; Zebrafish Proteins</subject><ispartof>Nature cell biology, 2005-11, Vol.7 (11), p.1124-1132</ispartof><rights>Springer Nature Limited 2005</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-8e7a9374b11d8a4d8c93130958aaa61cfcad54b7ca9238881ba2e5190c87ec163</citedby><cites>FETCH-LOGICAL-c466t-8e7a9374b11d8a4d8c93130958aaa61cfcad54b7ca9238881ba2e5190c87ec163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16244667$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiong, Wen-Cheng</creatorcontrib><creatorcontrib>Xie, Yi</creatorcontrib><creatorcontrib>Ding, Yu-Qiang</creatorcontrib><creatorcontrib>Hong, Yan</creatorcontrib><creatorcontrib>Feng, Zhu</creatorcontrib><creatorcontrib>Navarre, Sammy</creatorcontrib><creatorcontrib>Xi, Cai-Xia</creatorcontrib><creatorcontrib>Zhu, Xiao-Juan</creatorcontrib><creatorcontrib>Wang, Chun-Lei</creatorcontrib><creatorcontrib>Ackerman, S. L</creatorcontrib><creatorcontrib>Kozlowski, David</creatorcontrib><creatorcontrib>Mei, Lin</creatorcontrib><title>Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cells, Cultured</subject><subject>Cellular signal transduction</subject><subject>Chick Embryo - cytology</subject><subject>Chick Embryo - metabolism</subject><subject>Danio rerio</subject><subject>DCC Receptor</subject><subject>Developmental Biology</subject><subject>Humans</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Lipid Metabolism - physiology</subject><subject>Membrane proteins</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - physiology</subject><subject>Nerve Growth Factors - physiology</subject><subject>Netrin-1</subject><subject>Neurites - metabolism</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Phosphatidylinositol</subject><subject>Phosphatidylinositol 4,5-Diphosphate - metabolism</subject><subject>Phospholipid Transfer Proteins - metabolism</subject><subject>Phospholipid Transfer Proteins - physiology</subject><subject>Physiological aspects</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Stem Cells</subject><subject>Transfection</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumor Suppressor Proteins - physiology</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - physiology</subject><subject>Zebrafish Proteins</subject><issn>1465-7392</issn><issn>1476-4679</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0d1qFDEUAOBBLLZW8QmUAUHrxdRkkk0yl2VRW1iw-HMdzmTOzKbMJtskg_axfBGfySyzVRYKkov8fedwklMULyg5p4Sp9860lNX0UXFCuRQVF7J5vFuLRSVZUx8XT2O8IYRyTuST4piKmnMh5EkB12sft2tItrsbrfPRJj-WKYCLPYZyG3xC66rfv0rrSocp5A2trOsmg115vVqW0Q4Oxhw7lOC6bKZgE5Z-SkPwP9L6WXHUwxjx-X4-Lb5__PBteVmtPn-6Wl6sKpMrSZVCCQ2TvKW0U8A7ZRpGGWkWCgAENb2BbsFbaaCpmVKKtlDjgjbEKImGCnZavJnz5ppvJ4xJb2w0OI7g0E9Ri4Zw0Yj6v5BKIlWtdvD1DAcYUVvX-_wvZof1BVWMkVpxntX5AyqPDjfWeIe9zecHAe8OArJJ-DMNMMWor75-ObRvZ2uCjzFgr7fBbiDcaUr0rvN63_ksX-1fNbUb7P65faszOJtBzFduwKBv_BRy6-IDuV7O1EGaAv7NdX__B_YBv6M</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Xiong, Wen-Cheng</creator><creator>Xie, Yi</creator><creator>Ding, Yu-Qiang</creator><creator>Hong, Yan</creator><creator>Feng, Zhu</creator><creator>Navarre, Sammy</creator><creator>Xi, Cai-Xia</creator><creator>Zhu, Xiao-Juan</creator><creator>Wang, Chun-Lei</creator><creator>Ackerman, S. L</creator><creator>Kozlowski, David</creator><creator>Mei, Lin</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20051101</creationdate><title>Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth</title><author>Xiong, Wen-Cheng ; Xie, Yi ; Ding, Yu-Qiang ; Hong, Yan ; Feng, Zhu ; Navarre, Sammy ; Xi, Cai-Xia ; Zhu, Xiao-Juan ; Wang, Chun-Lei ; Ackerman, S. 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L</creatorcontrib><creatorcontrib>Kozlowski, David</creatorcontrib><creatorcontrib>Mei, Lin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiong, Wen-Cheng</au><au>Xie, Yi</au><au>Ding, Yu-Qiang</au><au>Hong, Yan</au><au>Feng, Zhu</au><au>Navarre, Sammy</au><au>Xi, Cai-Xia</au><au>Zhu, Xiao-Juan</au><au>Wang, Chun-Lei</au><au>Ackerman, S. L</au><au>Kozlowski, David</au><au>Mei, Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>7</volume><issue>11</issue><spage>1124</spage><epage>1132</epage><pages>1124-1132</pages><issn>1465-7392</issn><issn>1476-4679</issn><eissn>1476-4679</eissn><abstract>Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16244667</pmid><doi>10.1038/ncb1321</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Biomedical and Life Sciences Cancer Research Cell Biology Cells, Cultured Cellular signal transduction Chick Embryo - cytology Chick Embryo - metabolism Danio rerio DCC Receptor Developmental Biology Humans letter Life Sciences Lipid Metabolism - physiology Membrane proteins Membrane Proteins - metabolism Membrane Proteins - physiology Nerve Growth Factors - physiology Netrin-1 Neurites - metabolism Neurons - cytology Neurons - metabolism Phosphatidylinositol Phosphatidylinositol 4,5-Diphosphate - metabolism Phospholipid Transfer Proteins - metabolism Phospholipid Transfer Proteins - physiology Physiological aspects Receptors, Cell Surface - metabolism Signal Transduction - drug effects Stem Cells Transfection Tumor Suppressor Proteins - metabolism Tumor Suppressor Proteins - physiology Zebrafish - embryology Zebrafish - physiology Zebrafish Proteins |
| title | Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth |
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