Evidence in Support of Signaling Endosome-Based Retrograde Survival of Sympathetic Neurons
The mechanism by which target-derived Nerve Growth Factor (NGF) signaling is propagated retrogradely, over extremely long distances, to cell bodies to support survival of neurons is unclear. Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activi...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2003-07, Vol.39 (1), p.57-68 |
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| creator | Ye, Haihong Kuruvilla, Rejji Zweifel, Larry S Ginty, David D |
| description | The mechanism by which target-derived Nerve Growth Factor (NGF) signaling is propagated retrogradely, over extremely long distances, to cell bodies to support survival of neurons is unclear. Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor, TrkA, in both distal axons and cell bodies. In contrast, disruption of TrkA activity exclusively in proximal axonal segments affects neither retrograde NGF-TrkA signaling in cell bodies nor neuronal survival. Ligand-receptor internalization is necessary for survival of neurons supported by NGF on distal axons. Furthermore, antibody neutralization experiments indicate that retrogradely transported NGF, within cell bodies, is critical for neuronal survival but not for growth of distal axons. Taken together, our results indicate that retrogradely transported NGF-TrkA complexes promote sympathetic neuron survival. |
| doi_str_mv | 10.1016/S0896-6273(03)00266-6 |
| format | Article |
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Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor, TrkA, in both distal axons and cell bodies. In contrast, disruption of TrkA activity exclusively in proximal axonal segments affects neither retrograde NGF-TrkA signaling in cell bodies nor neuronal survival. Ligand-receptor internalization is necessary for survival of neurons supported by NGF on distal axons. Furthermore, antibody neutralization experiments indicate that retrogradely transported NGF, within cell bodies, is critical for neuronal survival but not for growth of distal axons. Taken together, our results indicate that retrogradely transported NGF-TrkA complexes promote sympathetic neuron survival.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/S0896-6273(03)00266-6</identifier><identifier>PMID: 12848932</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Axonal Transport - physiology ; Brain-derived neurotrophic factor ; Cell Compartmentation - physiology ; Cell Survival ; Cells, Cultured ; Endosomes - metabolism ; Endosomes - ultrastructure ; Experiments ; Infections ; Ligands ; Nerve Growth Factor - metabolism ; Neurons ; Neurons - metabolism ; Neurons - ultrastructure ; Phosphorylation ; Plasma ; Rats ; Receptor, trkA - metabolism ; Signal Transduction - physiology ; Studies ; Sympathetic Nervous System - cytology ; Sympathetic Nervous System - metabolism</subject><ispartof>Neuron (Cambridge, Mass.), 2003-07, Vol.39 (1), p.57-68</ispartof><rights>2003 Cell Press</rights><rights>Copyright Elsevier Limited Jul 3, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-deaa0369c617531486513e97f3a6f97c054d6fb61d1fbff751bedd1efa8babe63</citedby><cites>FETCH-LOGICAL-c533t-deaa0369c617531486513e97f3a6f97c054d6fb61d1fbff751bedd1efa8babe63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627303002666$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12848932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Haihong</creatorcontrib><creatorcontrib>Kuruvilla, Rejji</creatorcontrib><creatorcontrib>Zweifel, Larry S</creatorcontrib><creatorcontrib>Ginty, David D</creatorcontrib><title>Evidence in Support of Signaling Endosome-Based Retrograde Survival of Sympathetic Neurons</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>The mechanism by which target-derived Nerve Growth Factor (NGF) signaling is propagated retrogradely, over extremely long distances, to cell bodies to support survival of neurons is unclear. 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Taken together, our results indicate that retrogradely transported NGF-TrkA complexes promote sympathetic neuron survival.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Axonal Transport - physiology</subject><subject>Brain-derived neurotrophic factor</subject><subject>Cell Compartmentation - physiology</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Endosomes - metabolism</subject><subject>Endosomes - ultrastructure</subject><subject>Experiments</subject><subject>Infections</subject><subject>Ligands</subject><subject>Nerve Growth Factor - metabolism</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - ultrastructure</subject><subject>Phosphorylation</subject><subject>Plasma</subject><subject>Rats</subject><subject>Receptor, trkA - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Studies</subject><subject>Sympathetic Nervous System - cytology</subject><subject>Sympathetic Nervous System - metabolism</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0d-L1DAQB_Agiree_glKQRB9qGaaNG2eRI_1BxwKrr74EtJksuZom5q0C_ffm-4uCr4cBELgM5NhvoQ8BfoaKIg3O9pKUYqqYS8pe0VpJfLrHtkAlU3JQcr7ZPOXXJBHKd1QCryW8JBcQNXyVrJqQ35uD97iaLDwY7FbpinEuQiu2Pn9qHs_7ovtaEMKA5bvdUJbfMM5hn3UFjOPB3_Q_dHfDpOef-HsTfEFlxjG9Jg8cLpP-OR8X5IfH7bfrz6V118_fr56d12amrG5tKg1ZUIaAU3NgLeiBoaycUwLJxtDa26F6wRYcJ1zTQ0dWgvodNvpDgW7JC9OfacYfi-YZjX4ZLDv9YhhSaphnNOK8TshtI3kvKIZPv8P3oQl5n1kU-dZKYOjqk_KxJBSRKem6AcdbxVQtWakjhmpNQBF81kzUuu8z87dl25A-6_qHEoGb08A89YOHqNKxq8ZWR_RzMoGf8cXfwBvj6Ec</recordid><startdate>20030703</startdate><enddate>20030703</enddate><creator>Ye, Haihong</creator><creator>Kuruvilla, Rejji</creator><creator>Zweifel, Larry S</creator><creator>Ginty, David D</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030703</creationdate><title>Evidence in Support of Signaling Endosome-Based Retrograde Survival of Sympathetic Neurons</title><author>Ye, Haihong ; 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Apoptosis Axonal Transport - physiology Brain-derived neurotrophic factor Cell Compartmentation - physiology Cell Survival Cells, Cultured Endosomes - metabolism Endosomes - ultrastructure Experiments Infections Ligands Nerve Growth Factor - metabolism Neurons Neurons - metabolism Neurons - ultrastructure Phosphorylation Plasma Rats Receptor, trkA - metabolism Signal Transduction - physiology Studies Sympathetic Nervous System - cytology Sympathetic Nervous System - metabolism |
| title | Evidence in Support of Signaling Endosome-Based Retrograde Survival of Sympathetic Neurons |
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