{"corpus_id":205588314,"paper_sha":"48e81eab45b694f9e13c35cccad20be515acfe22","doi":"10.1038/s41598-017-08315-0","arxiv_id":null,"pmid":28801670,"pmcid":"5554145","mag_id":2744900448,"dblp_id":null,"acl_id":null,"title":"Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons","year":2017,"publication_date":"2017-08-11","venue":"Scientific Reports","journal":{"name":"Scientific Reports","pages":null,"volume":"7"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":32,"citation_count":16,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"ADAM10 Protein","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D000072197"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cell Adhesion Molecules, Neuronal","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D015816"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"GPI-Linked Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D058851"},{"d":"Ganglia, Spinal","mj":false,"qs":[{"q":"growth & development","mj":true,"ui":"Q000254"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D005727"},{"d":"Matrix Metalloproteinase Inhibitors","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D061965"},{"d":"Neural Cell Adhesion Molecules","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D019006"},{"d":"Neuronal Outgrowth","mj":false,"ui":"D000071446"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Tissue Inhibitor of Metalloproteinase-3","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D019717"}],"chemicals":[{"n":"Cell Adhesion Molecules, Neuronal","ui":"D015816","reg":"0"},{"n":"GPI-Linked Proteins","ui":"D058851","reg":"0"},{"n":"Matrix Metalloproteinase Inhibitors","ui":"D061965","reg":"0"},{"n":"Neural Cell Adhesion Molecules","ui":"D019006","reg":"0"},{"n":"Tissue Inhibitor of Metalloproteinase-3","ui":"D019717","reg":"0"},{"n":"limbic system-associated membrane protein","ui":"C095362","reg":"0"},{"n":"neurotrimin","ui":"C092530","reg":"0"},{"n":"ADAM10 Protein","ui":"D000072197","reg":"EC 3.4.24.81"},{"n":"ADAM10 protein, rat","ui":"C542371","reg":"EC 3.4.24.81"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/s41598-017-08315-0.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/48e81eab45b694f9e13c35cccad20be515acfe22","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.","claims":[{"public_id":"cl_2a162aec12c4dd765478485869d20eac","status":"active","text":"ADAM-dependent shedding of cell surface limbic system-associated membrane protein promotes outgrowth from dorsal root ganglion neurons.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_2a162aec12c4dd765478485869d20eac"},{"public_id":"cl_68b2e2287ed16f3ed0bbfea9979edc36","status":"active","text":"Loss of limbic system-associated membrane protein decreases the sensitivity of neurite outgrowth to ADAM10 inhibition.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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