Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System
The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disinteg...
Gespeichert in:
| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2015-11, Vol.74 (11), p.1077-1085 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1085 |
|---|---|
| container_issue | 11 |
| container_start_page | 1077 |
| container_title | Journal of neuropathology and experimental neurology |
| container_volume | 74 |
| creator | Horste, Gerd Meyer zu Derksen, Angelika Stassart, Ruth Szepanowski, Fabian Thanos, Melissa Stettner, Mark Boettcher, Christina Lehmann, Helmar C. Hartung, Hans-Peter Kieseier, Bernd C. |
| description | The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination.A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type–specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases. |
| doi_str_mv | 10.1097/NEN.0000000000000253 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1722924590</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1097/NEN.0000000000000253</oup_id><sourcerecordid>1722924590</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6293-925b625fe9061b893546bfd8e9edfaf8c2c3ac54accbb2d1eaaffb396d2ced0b3</originalsourceid><addsrcrecordid>eNqNkEtPwzAQhC0EgvL4Bwj5yCXgOLEbH6vylKAgAefIdtYk4MTFdij99wQVEOICe1lp9c3saBDaT8lRSsT4eHY6OyI_h7JsDY1SxvKEs3GxjkbDjSYZ4WILbYfwNDCCiHwTbVGeU055MUIwg967Tlo8OZlcpwTfete6CAHf9PHRu0WssTP4rpXWJlNpGwUeXy_BNp2MUOHJm-sCbjoca8C34Jt5DX5wm4F_dX3Ad8sQod1FG0baAHufewc9nJ3eTy-Sq5vzy-nkKtGciiwRlClOmQFBeKoKkbGcK1MVIKAy0hSa6kxqlkutlaJVClIaozLBK6qhIirbQYcr37l3Lz2EWLZN0GCt7GBIU6ZjSgXNmSADmq9Q7V0IHkw5900r_bJMSflRcDkUXP4ueJAdfH7oVQvVt-ir0QEoVsDC2Qg-PNt-Ab6sQdpY_-V9vJK6fv6_NO_w8ZXp</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1722924590</pqid></control><display><type>article</type><title>Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System</title><source>Oxford University Press Journals</source><source>MEDLINE</source><source>EZB Electronic Journals Library</source><source>Journals@Ovid Complete</source><creator>Horste, Gerd Meyer zu ; Derksen, Angelika ; Stassart, Ruth ; Szepanowski, Fabian ; Thanos, Melissa ; Stettner, Mark ; Boettcher, Christina ; Lehmann, Helmar C. ; Hartung, Hans-Peter ; Kieseier, Bernd C.</creator><creatorcontrib>Horste, Gerd Meyer zu ; Derksen, Angelika ; Stassart, Ruth ; Szepanowski, Fabian ; Thanos, Melissa ; Stettner, Mark ; Boettcher, Christina ; Lehmann, Helmar C. ; Hartung, Hans-Peter ; Kieseier, Bernd C.</creatorcontrib><description>The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination.A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type–specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1097/NEN.0000000000000253</identifier><identifier>PMID: 26426268</identifier><language>eng</language><publisher>England: American Association of Neuropathologists, Inc</publisher><subject>Action Potentials - genetics ; ADAM Proteins - deficiency ; ADAM Proteins - genetics ; ADAM10 Protein ; Amyloid Precursor Protein Secretases - deficiency ; Amyloid Precursor Protein Secretases - genetics ; Animals ; Axons - physiology ; Disease Models, Animal ; Ganglia, Spinal - cytology ; Hand Strength - physiology ; In Vitro Techniques ; Membrane Proteins - deficiency ; Membrane Proteins - genetics ; Mice ; Mice, Transgenic ; Microscopy, Electron ; Motor Neurons - cytology ; Nerve Fibers, Myelinated - physiology ; Nerve Regeneration - genetics ; Neural Conduction - genetics ; Organ Culture Techniques ; Peripheral Nervous System - cytology ; Peripheral Nervous System - physiology ; Sciatic Nerve - pathology ; Sciatic Nerve - ultrastructure ; Sciatic Neuropathy - genetics ; Sciatic Neuropathy - pathology ; Sciatic Neuropathy - physiopathology</subject><ispartof>Journal of neuropathology and experimental neurology, 2015-11, Vol.74 (11), p.1077-1085</ispartof><rights>Copyright © 2015 by the American Association of Neuropathologists, Inc. 2015</rights><rights>2015 by American Association of Neuropathologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6293-925b625fe9061b893546bfd8e9edfaf8c2c3ac54accbb2d1eaaffb396d2ced0b3</citedby><cites>FETCH-LOGICAL-c6293-925b625fe9061b893546bfd8e9edfaf8c2c3ac54accbb2d1eaaffb396d2ced0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26426268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horste, Gerd Meyer zu</creatorcontrib><creatorcontrib>Derksen, Angelika</creatorcontrib><creatorcontrib>Stassart, Ruth</creatorcontrib><creatorcontrib>Szepanowski, Fabian</creatorcontrib><creatorcontrib>Thanos, Melissa</creatorcontrib><creatorcontrib>Stettner, Mark</creatorcontrib><creatorcontrib>Boettcher, Christina</creatorcontrib><creatorcontrib>Lehmann, Helmar C.</creatorcontrib><creatorcontrib>Hartung, Hans-Peter</creatorcontrib><creatorcontrib>Kieseier, Bernd C.</creatorcontrib><title>Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination.A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type–specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.</description><subject>Action Potentials - genetics</subject><subject>ADAM Proteins - deficiency</subject><subject>ADAM Proteins - genetics</subject><subject>ADAM10 Protein</subject><subject>Amyloid Precursor Protein Secretases - deficiency</subject><subject>Amyloid Precursor Protein Secretases - genetics</subject><subject>Animals</subject><subject>Axons - physiology</subject><subject>Disease Models, Animal</subject><subject>Ganglia, Spinal - cytology</subject><subject>Hand Strength - physiology</subject><subject>In Vitro Techniques</subject><subject>Membrane Proteins - deficiency</subject><subject>Membrane Proteins - genetics</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Electron</subject><subject>Motor Neurons - cytology</subject><subject>Nerve Fibers, Myelinated - physiology</subject><subject>Nerve Regeneration - genetics</subject><subject>Neural Conduction - genetics</subject><subject>Organ Culture Techniques</subject><subject>Peripheral Nervous System - cytology</subject><subject>Peripheral Nervous System - physiology</subject><subject>Sciatic Nerve - pathology</subject><subject>Sciatic Nerve - ultrastructure</subject><subject>Sciatic Neuropathy - genetics</subject><subject>Sciatic Neuropathy - pathology</subject><subject>Sciatic Neuropathy - physiopathology</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtPwzAQhC0EgvL4Bwj5yCXgOLEbH6vylKAgAefIdtYk4MTFdij99wQVEOICe1lp9c3saBDaT8lRSsT4eHY6OyI_h7JsDY1SxvKEs3GxjkbDjSYZ4WILbYfwNDCCiHwTbVGeU055MUIwg967Tlo8OZlcpwTfete6CAHf9PHRu0WssTP4rpXWJlNpGwUeXy_BNp2MUOHJm-sCbjoca8C34Jt5DX5wm4F_dX3Ad8sQod1FG0baAHufewc9nJ3eTy-Sq5vzy-nkKtGciiwRlClOmQFBeKoKkbGcK1MVIKAy0hSa6kxqlkutlaJVClIaozLBK6qhIirbQYcr37l3Lz2EWLZN0GCt7GBIU6ZjSgXNmSADmq9Q7V0IHkw5900r_bJMSflRcDkUXP4ueJAdfH7oVQvVt-ir0QEoVsDC2Qg-PNt-Ab6sQdpY_-V9vJK6fv6_NO_w8ZXp</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Horste, Gerd Meyer zu</creator><creator>Derksen, Angelika</creator><creator>Stassart, Ruth</creator><creator>Szepanowski, Fabian</creator><creator>Thanos, Melissa</creator><creator>Stettner, Mark</creator><creator>Boettcher, Christina</creator><creator>Lehmann, Helmar C.</creator><creator>Hartung, Hans-Peter</creator><creator>Kieseier, Bernd C.</creator><general>American Association of Neuropathologists, Inc</general><general>by American Association of Neuropathologists, 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>201511</creationdate><title>Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System</title><author>Horste, Gerd Meyer zu ; Derksen, Angelika ; Stassart, Ruth ; Szepanowski, Fabian ; Thanos, Melissa ; Stettner, Mark ; Boettcher, Christina ; Lehmann, Helmar C. ; Hartung, Hans-Peter ; Kieseier, Bernd C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6293-925b625fe9061b893546bfd8e9edfaf8c2c3ac54accbb2d1eaaffb396d2ced0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Action Potentials - genetics</topic><topic>ADAM Proteins - deficiency</topic><topic>ADAM Proteins - genetics</topic><topic>ADAM10 Protein</topic><topic>Amyloid Precursor Protein Secretases - deficiency</topic><topic>Amyloid Precursor Protein Secretases - genetics</topic><topic>Animals</topic><topic>Axons - physiology</topic><topic>Disease Models, Animal</topic><topic>Ganglia, Spinal - cytology</topic><topic>Hand Strength - physiology</topic><topic>In Vitro Techniques</topic><topic>Membrane Proteins - deficiency</topic><topic>Membrane Proteins - genetics</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Electron</topic><topic>Motor Neurons - cytology</topic><topic>Nerve Fibers, Myelinated - physiology</topic><topic>Nerve Regeneration - genetics</topic><topic>Neural Conduction - genetics</topic><topic>Organ Culture Techniques</topic><topic>Peripheral Nervous System - cytology</topic><topic>Peripheral Nervous System - physiology</topic><topic>Sciatic Nerve - pathology</topic><topic>Sciatic Nerve - ultrastructure</topic><topic>Sciatic Neuropathy - genetics</topic><topic>Sciatic Neuropathy - pathology</topic><topic>Sciatic Neuropathy - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horste, Gerd Meyer zu</creatorcontrib><creatorcontrib>Derksen, Angelika</creatorcontrib><creatorcontrib>Stassart, Ruth</creatorcontrib><creatorcontrib>Szepanowski, Fabian</creatorcontrib><creatorcontrib>Thanos, Melissa</creatorcontrib><creatorcontrib>Stettner, Mark</creatorcontrib><creatorcontrib>Boettcher, Christina</creatorcontrib><creatorcontrib>Lehmann, Helmar C.</creatorcontrib><creatorcontrib>Hartung, Hans-Peter</creatorcontrib><creatorcontrib>Kieseier, Bernd C.</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>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horste, Gerd Meyer zu</au><au>Derksen, Angelika</au><au>Stassart, Ruth</au><au>Szepanowski, Fabian</au><au>Thanos, Melissa</au><au>Stettner, Mark</au><au>Boettcher, Christina</au><au>Lehmann, Helmar C.</au><au>Hartung, Hans-Peter</au><au>Kieseier, Bernd C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2015-11</date><risdate>2015</risdate><volume>74</volume><issue>11</issue><spage>1077</spage><epage>1085</epage><pages>1077-1085</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination.A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type–specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.</abstract><cop>England</cop><pub>American Association of Neuropathologists, Inc</pub><pmid>26426268</pmid><doi>10.1097/NEN.0000000000000253</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3069 |
| ispartof | Journal of neuropathology and experimental neurology, 2015-11, Vol.74 (11), p.1077-1085 |
| issn | 0022-3069 1554-6578 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1722924590 |
| source | Oxford University Press Journals; MEDLINE; EZB Electronic Journals Library; Journals@Ovid Complete |
| subjects | Action Potentials - genetics ADAM Proteins - deficiency ADAM Proteins - genetics ADAM10 Protein Amyloid Precursor Protein Secretases - deficiency Amyloid Precursor Protein Secretases - genetics Animals Axons - physiology Disease Models, Animal Ganglia, Spinal - cytology Hand Strength - physiology In Vitro Techniques Membrane Proteins - deficiency Membrane Proteins - genetics Mice Mice, Transgenic Microscopy, Electron Motor Neurons - cytology Nerve Fibers, Myelinated - physiology Nerve Regeneration - genetics Neural Conduction - genetics Organ Culture Techniques Peripheral Nervous System - cytology Peripheral Nervous System - physiology Sciatic Nerve - pathology Sciatic Nerve - ultrastructure Sciatic Neuropathy - genetics Sciatic Neuropathy - pathology Sciatic Neuropathy - physiopathology |
| title | Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T23%3A09%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neuronal%20ADAM10%20Promotes%20Outgrowth%20of%20Small-Caliber%20Myelinated%20Axons%20in%20the%20Peripheral%20Nervous%20System&rft.jtitle=Journal%20of%20neuropathology%20and%20experimental%20neurology&rft.au=Horste,%20Gerd%20Meyer%20zu&rft.date=2015-11&rft.volume=74&rft.issue=11&rft.spage=1077&rft.epage=1085&rft.pages=1077-1085&rft.issn=0022-3069&rft.eissn=1554-6578&rft_id=info:doi/10.1097/NEN.0000000000000253&rft_dat=%3Cproquest_cross%3E1722924590%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1722924590&rft_id=info:pmid/26426268&rft_oup_id=10.1097/NEN.0000000000000253&rfr_iscdi=true |